首页 期刊 论文 学科刊群 资讯 加盟 关于
EN
image
Article(id=1308467769691894227, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1308467640138227885, articleNumber=null, orderNo=null, doi=10.16438/j.0513-4870.2025-0697, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1750348800000, receivedDateStr=2025-06-20, revisedDate=1754236800000, revisedDateStr=2025-08-04, acceptedDate=null, acceptedDateStr=null, onlineDate=1789892626450, onlineDateStr=2026-09-20, pubDate=1760198400000, pubDateStr=2025-10-12, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1789892626450, onlineIssueDateStr=2026-09-20, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1789892626450, creator=13701087609, updateTime=1789892626450, updator=13701087609, issue=Issue{id=1308467640138227885, tenantId=1146029695717560320, journalId=1189982191388893191, year='2025', volume='60', issue='10', pageStart='2913', pageEnd='3262', issueExtLink='null', onlineDate='null', pubDate='1760198400000', pubDateStr='2025-10-12', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1789892595562, creator='13701087609', updateTime=1789893273356, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1308470483071033443, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1308467640138227885, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1308470483071033444, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1308467640138227885, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=3229, endPage=3237, ext={EN=ArticleExt(id=1308467769905803732, articleId=1308467769691894227, tenantId=1146029695717560320, journalId=1189982191388893191, language=EN, title=Iron-galloflavin self-assembled platform with triple synergistic mechanisms for the treatment of triple-negative breast cancer, columnId=1190335348761793317, journalTitle=Acta Pharmaceutica Sinica, columnName=Original Articles, runingTitle=null, highlight=null, articleAbstract=

Triple-negative breast cancer (TNBC) is characterized by high invasiveness, a high risk of recurrence and metastasis, and poor prognosis. The accumulation of lactate in the tumor microenvironment produced by tumor cell glycolysis is a key factor driving the malignant progression of TNBC. In this study, we developed a lactate metabolism-regulating self-assembled galloflavin-Fe lipid peroxidation accelerator (SGF) to inhibit the growth of TNBC. The system was constructed by coordinating iron ions with the hydroxyl groups of galloflavin to form a metal-polyphenol network, which encapsulates the drug sorafenib. By adjusting the drug loading ratio of sorafenib to galloflavin at 1:1, SGF nanoparticles with a size of 136.20 ± 0.83 nm and a polydispersity index of 0.103 ± 0.012 were prepared, achieving efficient co-loading of both drugs. The metal-polyphenol network of SGF exhibits photothermal conversion properties, generating localized heat under 808 nm laser irradiation, effectively killing tumor cells. Under the low pH conditions of the tumor microenvironment and lysosomes, iron ions and galloflavin dissociate to release sorafenib, accelerating the Fenton reaction through iron ion supplementation and glutathione downregulation, which cooperatively promotes lipid peroxidation in tumor cells. Furthermore, galloflavin inhibits lactate dehydrogenase A, downregulating the conversion of pyruvate to lactate and reducing lactate production, thereby improving the acidic tumor microenvironment and efficiently suppressing the progression of TNBC. The SGF nanosystem designed and constructed in this study integrates three synergistic mechanisms-photothermal effect, lipid peroxidation induction, and lactate metabolism regulation to provide a synergistic and precise strike against TNBC and its high-lactate microenvironment, offering a new therapeutic strategy to improve the clinical prognosis of this highly invasive cancer.

, authors=Hai-qing YU, Tian-jiao ZHOU, Yan WANG, Hao-bin CHE, Jia-wen RU, Hu-lin JIANG*, authorsList=Hai-qing YU, Tian-jiao ZHOU, Yan WANG, Hao-bin CHE, Jia-wen RU, Hu-lin JIANG, authorCompany=null, correspAuthors=Hu-lin JIANG, authorNote=null, correspAuthorsNote=null, copyrightStatement=Copyright ©2025 Acta Pharmaceutica Sinica. All rights reserved., copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1308467773236081125, articleId=1308467769691894227, tenantId=1146029695717560320, journalId=1189982191388893191, language=CN, title=铁-没食子黄素自组装平台三重协同机制在三阴性乳腺癌治疗中的应用, columnId=1190335348896011050, journalTitle=药学学报, columnName=研究论文, runingTitle=null, highlight=null, articleAbstract=

三阴性乳腺癌侵袭性强、复发转移风险高且预后较差, 其中肿瘤细胞糖酵解导致的乳酸堆积是驱动三阴性乳腺癌恶性进展的关键因素。本研究据此构建了一种调控乳酸代谢的铁-没食子黄素自组装脂质过氧化加速器(self-assembled galloflavin-Fe lipid peroxidation accelerator, SGF) 用于抑制三阴性乳腺癌的生长。该体系由铁离子和没食子黄素酚羟基配位形成金属多酚网络装载药物索拉非尼制备得到。通过调整索拉非尼与没食子黄素的投料比为1:1, 制备得到粒径为136.20 ± 0.83 nm, 多分散系数为0.103 ± 0.012的SGF纳米粒, 实现双药协同装载。SGF的金属-多酚网络具有光热转换性能, 在808 nm光照射下可产生局部高热, 有效杀伤肿瘤细胞。在肿瘤微环境和溶酶体低pH条件下, 铁离子和没食子黄素解离释放药物索拉非尼, 借助铁离子补充和谷胱甘肽下调加速芬顿反应进行, 协同促进肿瘤细胞脂质过氧化进程; 没食子黄素通过抑制乳酸脱氢酶A, 下调丙酮酸向乳酸的转化, 减少乳酸生成, 从而改善肿瘤组织酸性微环境, 高效抑制三阴性乳腺癌的进展。本课题设计并构建的SGF纳米平台集光热效应、脂质过氧化诱导及乳酸代谢调控三重机制, 实现对三阴性乳腺癌及其高乳酸微环境的协同精准打击, 旨在为改善此类高度侵袭性乳腺癌的临床预后提供新的治疗策略。

, authors=余海晴, 周天娇, 王琰, 车昊滨, 茹佳雯, 姜虎林*, authorsList=余海晴, 周天娇, 王琰, 车昊滨, 茹佳雯, 姜虎林, authorCompany=null, correspAuthors=姜虎林, authorNote=

作者贡献:

余海晴承担了主要实验工作, 并撰写论文初稿; 周天娇负责研究设计, 稿件审阅与修改; 王琰参与了实验操作、数据整理和论文修改; 车昊滨和茹佳雯参与了实验操作与数据整理; 姜虎林为本研究的通讯作者, 统筹课题执行, 并对论文进行全面修改与定稿。所有作者均阅读并同意最终稿内容。

, correspAuthorsNote=
姜虎林, E-mail:
, copyrightStatement=版权所有©《药学学报》编辑部2025, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=N8aUmeslXoUSzEUGKG2NLg==, magXml=XyDAwukuIqyruNbBgJe8aA==, pdfUrl=null, pdf=nOAj3Ysb+uxC2sfeAJNLhg==, pdfFileSize=3687698, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=4NBmSDG+geWKg7ONneX1+Q==, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=yqUCOfEvq6VAhdHRR6PWVA==, mapNumber=null, fund=null)}, authors=[Author(id=1308498054173524559, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, orderNo=0, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1308498054249022033, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, authorId=1308498054173524559, language=EN, stringName=Hai-qing YU, firstName=Hai-qing, middleName=null, lastName=YU, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1308498054328713810, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, authorId=1308498054173524559, language=CN, stringName=余海晴, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=中国药科大学药学院, 江苏 南京 210009, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1308498054077055563, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, xref=null, ext=[AuthorCompanyExt(id=1308498054089638476, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, companyId=1308498054077055563, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China), AuthorCompanyExt(id=1308498054102221389, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, companyId=1308498054077055563, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=中国药科大学药学院, 江苏 南京 210009)])]), Author(id=1308498054404211284, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, orderNo=1, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1308498054479708758, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, authorId=1308498054404211284, language=EN, stringName=Tian-jiao ZHOU, firstName=Tian-jiao, middleName=null, lastName=ZHOU, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1308498054555206231, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, authorId=1308498054404211284, language=CN, stringName=周天娇, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=中国药科大学药学院, 江苏 南京 210009, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1308498054077055563, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, xref=null, ext=[AuthorCompanyExt(id=1308498054089638476, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, companyId=1308498054077055563, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China), AuthorCompanyExt(id=1308498054102221389, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, companyId=1308498054077055563, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=中国药科大学药学院, 江苏 南京 210009)])]), Author(id=1308498054626509401, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, orderNo=2, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1308498054706201179, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, authorId=1308498054626509401, language=EN, stringName=Yan WANG, firstName=Yan, middleName=null, lastName=WANG, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1308498056409088604, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, authorId=1308498054626509401, language=CN, stringName=王琰, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=中国药科大学药学院, 江苏 南京 210009, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1308498054077055563, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, xref=null, ext=[AuthorCompanyExt(id=1308498054089638476, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, companyId=1308498054077055563, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China), AuthorCompanyExt(id=1308498054102221389, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, companyId=1308498054077055563, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=中国药科大学药学院, 江苏 南京 210009)])]), Author(id=1308498056488780382, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, orderNo=3, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1308498056564277856, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, authorId=1308498056488780382, language=EN, stringName=Hao-bin CHE, firstName=Hao-bin, middleName=null, lastName=CHE, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1308498056643969633, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, authorId=1308498056488780382, language=CN, stringName=车昊滨, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=中国药科大学药学院, 江苏 南京 210009, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1308498054077055563, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, xref=null, ext=[AuthorCompanyExt(id=1308498054089638476, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, companyId=1308498054077055563, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China), AuthorCompanyExt(id=1308498054102221389, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, companyId=1308498054077055563, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=中国药科大学药学院, 江苏 南京 210009)])]), Author(id=1308498056715272803, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, orderNo=4, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1308498056807547493, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, authorId=1308498056715272803, language=EN, stringName=Jia-wen RU, firstName=Jia-wen, middleName=null, lastName=RU, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1308498056866267750, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, authorId=1308498056715272803, language=CN, stringName=茹佳雯, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=中国药科大学药学院, 江苏 南京 210009, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1308498054077055563, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, xref=null, ext=[AuthorCompanyExt(id=1308498054089638476, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, companyId=1308498054077055563, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China), AuthorCompanyExt(id=1308498054102221389, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, companyId=1308498054077055563, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=中国药科大学药学院, 江苏 南京 210009)])]), Author(id=1308498056929182312, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, orderNo=5, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=jianghulin3@163.com, emailSecond=null, emailThird=null, correspondingAuthor=1, authorType=1, ext={EN=AuthorExt(id=1308498057000485482, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, authorId=1308498056929182312, language=EN, stringName=Hu-lin JIANG, firstName=Hu-lin, middleName=null, lastName=JIANG, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=*, address=School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1308498057067594347, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, authorId=1308498056929182312, language=CN, stringName=姜虎林, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=*, address=中国药科大学药学院, 江苏 南京 210009, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1308498054077055563, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, xref=null, ext=[AuthorCompanyExt(id=1308498054089638476, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, companyId=1308498054077055563, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China), AuthorCompanyExt(id=1308498054102221389, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, companyId=1308498054077055563, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=中国药科大学药学院, 江苏 南京 210009)])])], keywords=[Keyword(id=1308498057197617772, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, language=EN, orderNo=1, keyword=triple-negative breast cancer), Keyword(id=1308498057268920941, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, language=EN, orderNo=2, keyword=sorafenib), Keyword(id=1308498057340224110, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, language=EN, orderNo=3, keyword=galloflavin), Keyword(id=1308498057411527279, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, language=EN, orderNo=4, keyword=metal-polyphenol network), Keyword(id=1308498057487024752, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, language=EN, orderNo=5, keyword=lipid peroxidation), Keyword(id=1308498057566716529, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, language=CN, orderNo=1, keyword=三阴性乳腺癌), Keyword(id=1308498057642214002, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, language=CN, orderNo=2, keyword=索拉非尼), Keyword(id=1308498057717711475, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, language=CN, orderNo=3, keyword=没食子黄素), Keyword(id=1308498057776431732, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, language=CN, orderNo=4, keyword=金属多酚网络), Keyword(id=1308498057847734901, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, language=CN, orderNo=5, keyword=脂质过氧化)], refs=[Reference(id=1308498061379338890, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=1, rfOrder=0, authorNames=null, journalName=null, refType=null, unstructuredReference=França GS, Baron M, King BR, et al. Cellular adaptation to cancer therapy along a resistance continuum [J]. Nature, 2024, 631: 876-883., articleTitle=null, refAbstract=null), Reference(id=1308498061467419275, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=2, rfOrder=1, authorNames=null, journalName=null, refType=null, unstructuredReference=Klein CA. Selection and adaptation during metastatic cancer progression [J]. Nature, 2013, 501: 365-372., articleTitle=null, refAbstract=null), Reference(id=1308498061559693964, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=3, rfOrder=2, authorNames=null, journalName=null, refType=null, unstructuredReference=Siegel RL, Kratzer TB, Giaquinto AN, et al. Cancer statistics, 2025 [J]. Ca Cancer J Clin, 2025, 75: 10-45., articleTitle=null, refAbstract=null), Reference(id=1308498061626802829, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=4, rfOrder=3, authorNames=null, journalName=null, refType=null, unstructuredReference=Yin L, Duan JJ, Bian XW, et al. Triple-negative breast cancer molecular subtyping and treatment progress [J]. Breast Cancer Res, 2020, 22: 61., articleTitle=null, refAbstract=null), Reference(id=1308498061706494606, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=5, rfOrder=4, authorNames=null, journalName=null, refType=null, unstructuredReference=Bianchini G, De Angelis C, Licata L, et al. Treatment landscape of triple-negative breast cancer-expanded options, evolving needs [J]. Nat Rev Clin Oncol, 2022, 19: 91-113., articleTitle=null, refAbstract=null), Reference(id=1308498061786186383, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=6, rfOrder=5, authorNames=null, journalName=null, refType=null, unstructuredReference=Fendt SM. 100 years of the Warburg effect: a cancer metabolism endeavor [J]. Cell, 2024, 187: 3824-3828., articleTitle=null, refAbstract=null), Reference(id=1308498061870072464, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=7, rfOrder=6, authorNames=null, journalName=null, refType=null, unstructuredReference=Swietach P, Boedtkjer E, Pedersen SF. How protons pave the way to aggressive cancers [J]. Nat Rev Cancer, 2023, 23: 825-841., articleTitle=null, refAbstract=null), Reference(id=1308498061937181329, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=8, rfOrder=7, authorNames=null, journalName=null, refType=null, unstructuredReference=Liu XD, Li SJ, Cui QH, et al. Activation of GPR81 by lactate drives tumour-induced cachexia [J]. Nat Metab, 2024, 6: 708-723., articleTitle=null, refAbstract=null), Reference(id=1308498062012678802, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=9, rfOrder=8, authorNames=null, journalName=null, refType=null, unstructuredReference=Wang N, Zhu MJ, Jiang YM, et al. Neutrophil-mediated tumor discrimination biomimetic nanodevice for precise tumor eradication and metastasis cascade perturbing [J]. ACS Appl Mater Interfaces, 2025, 17: 23680-23690., articleTitle=null, refAbstract=null), Reference(id=1308498062083981971, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=10, rfOrder=9, authorNames=null, journalName=null, refType=null, unstructuredReference=Bohn T, Rapp S, Luther N, et al. Tumor immunoevasion via acidosis-dependent induction of regulatory tumor-associated macrophages [J]. Nat Immunol, 2018, 19: 1319-1329., articleTitle=null, refAbstract=null), Reference(id=1308498062146896532, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=11, rfOrder=10, authorNames=null, journalName=null, refType=null, unstructuredReference=Zhao PR, Li HY, Bu WB. A forward vision for chemodynamic therapy: issues and opportunities [J]. Angew Chem Int Ed Engl, 2023, 62: e202210415., articleTitle=null, refAbstract=null), Reference(id=1308498062218199701, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=12, rfOrder=11, authorNames=null, journalName=null, refType=null, unstructuredReference=Wu JY, Meng Y, Wu F, et al. Ultrasound-driven non-metallic fenton-active center construction for extensive chemodynamic therapy [J]. Adv Mater, 2024, 36: e2307980., articleTitle=null, refAbstract=null), Reference(id=1308498062306280086, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=13, rfOrder=12, authorNames=null, journalName=null, refType=null, unstructuredReference=Xing Y, Xiu JD, Zhou MY, et al. Copper single-atom jellyfish-like nanomotors for enhanced tumor penetration and nanocatalytic therapy [J]. ACS Nano, 2023, 17: 6789-6799., articleTitle=null, refAbstract=null), Reference(id=1308498062373388951, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=14, rfOrder=13, authorNames=null, journalName=null, refType=null, unstructuredReference=Zhou TJ, Xu Y, Xing L, et al. A harmless-harmful switchable and uninterrupted laccase-instructed killer for activatable chemodynamic therapy [J]. Adv Mater, 2021, 33: e2100114., articleTitle=null, refAbstract=null), Reference(id=1308498062444692120, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=15, rfOrder=14, authorNames=null, journalName=null, refType=null, unstructuredReference=Michalek RD, Gerriets VA, Jacobs SR, et al. Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets [J]. J Immunol, 2011, 186: 3299-3303., articleTitle=null, refAbstract=null), Reference(id=1308498062507606681, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=16, rfOrder=15, authorNames=null, journalName=null, refType=null, unstructuredReference=Hirschhaeuser F, Sattler UG, Mueller-Klieser W. Lactate: a metabolic key player in cancer [J]. Cancer Res, 2011, 71: 6921-6925., articleTitle=null, refAbstract=null), Reference(id=1308498062570521242, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=17, rfOrder=16, authorNames=null, journalName=null, refType=null, unstructuredReference=Zhou TJ, Wan X, Zhang MM, et al. Tumor microenvironment-initiated lipid redox cycling for efficient triple-negative breast cancer therapy [J]. Biomaterials, 2023, 300: 122205., articleTitle=null, refAbstract=null), Reference(id=1308498062662795931, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=18, rfOrder=17, authorNames=null, journalName=null, refType=null, unstructuredReference=Thompson KH, Orvig C. Boon and bane of metal ions in medicine [J]. Science, 2003, 300: 936-939., articleTitle=null, refAbstract=null), Reference(id=1308498062729904796, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=19, rfOrder=18, authorNames=null, journalName=null, refType=null, unstructuredReference=Ejima H, Richardson JJ, Liang K, et al. One-step assembly of coordination complexes for versatile film and particle engineering [J]. Science, 2013, 341: 154-157., articleTitle=null, refAbstract=null), Reference(id=1308498062797013661, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=20, rfOrder=19, authorNames=null, journalName=null, refType=null, unstructuredReference=Guo JL, Ping Y, Ejima H, et al. Engineering multifunctional capsules through the assembly of metal-phenolic networks [J]. Angew Chem Int Ed Engl, 2014, 53: 5546-5551., articleTitle=null, refAbstract=null), Reference(id=1308498062868316830, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=21, rfOrder=20, authorNames=null, journalName=null, refType=null, unstructuredReference=Farabegoli F, Vettraino M, Manerba M, et al. Galloflavin, a new lactate dehydrogenase inhibitor, induces the death of human breast cancer cells with different glycolytic attitude by affecting distinct signaling pathways [J]. Eur J Pharm Sci, 2012, 47: 729-738., articleTitle=null, refAbstract=null), Reference(id=1308498062943814303, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=22, rfOrder=21, authorNames=null, journalName=null, refType=null, unstructuredReference=Zhang Z, Li XN, Liu WQ, et al. Polyphenol nanocomplex modulates lactate metabolic reprogramming and elicits immune responses to enhance cancer therapeutic effect [J]. Drug Resist Updat, 2024, 73: 101060., articleTitle=null, refAbstract=null), Reference(id=1308498063015117472, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=23, rfOrder=22, authorNames=null, journalName=null, refType=null, unstructuredReference=Zhou Y, Ke P, Bao XY, et al. Peptide nano-blanket impedes fibroblasts activation and subsequent formation of pre-metastatic niche [J]. Nat Commun, 2022, 13: 2906., articleTitle=null, refAbstract=null), Reference(id=1308498063086420641, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=24, rfOrder=23, authorNames=null, journalName=null, refType=null, unstructuredReference=Manerba M, Vettraino M, Fiume L, et al. Galloflavin (CAS 568-80-9): a novel inhibitor of lactate dehydrogenase [J]. ChemMedChem, 2012, 7: 311-317., articleTitle=null, refAbstract=null), Reference(id=1308498063170306722, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=25, rfOrder=24, authorNames=null, journalName=null, refType=null, unstructuredReference=Zhou TJ, Zhang MM, Liu DM, et al. Glutathione depletion and dihydroorotate dehydrogenase inhibition actuated ferroptosis-augment to surmount triple-negative breast cancer [J]. Biomaterials, 2024, 305: 122447., articleTitle=null, refAbstract=null), Reference(id=1308498063249998499, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=26, rfOrder=25, authorNames=null, journalName=null, refType=null, unstructuredReference=He YJ, Liu XY, Xing L, et al. Fenton reaction-independent ferroptosis therapy via glutathione and iron redox couple sequentially triggered lipid peroxide generator [J]. Biomaterials, 2020, 241: 119911., articleTitle=null, refAbstract=null), Reference(id=1308498063317107364, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=27, rfOrder=26, authorNames=null, journalName=null, refType=null, unstructuredReference=Fiume L, Manerba M, Vettraino M, et al. Effect of sorafenib on the energy metabolism of hepatocellular carcinoma cells [J]. Eur J Pharmacol, 2011, 670: 39-43., articleTitle=null, refAbstract=null)], funds=null, companyList=[AuthorCompany(id=1308498054077055563, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, xref=null, ext=[AuthorCompanyExt(id=1308498054089638476, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, companyId=1308498054077055563, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China), AuthorCompanyExt(id=1308498054102221389, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, companyId=1308498054077055563, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=中国药科大学药学院, 江苏 南京 210009)])], figs=[ArticleFig(id=1308498058019701366, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, language=EN, label=null, caption=null, figureFileSmall=daDu2+YAbSNgQ4+mxwQ7mw==, figureFileBig=U6XFCr3FIcjH3Ig/+Ja94w==, tableContent=null), ArticleFig(id=1308498058078421623, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, language=CN, label=Fig.1, caption=Triple-synergistic mechanism of self-assembled galloflavin-Fe lipid peroxidation accelerator (SGF) nanosystem for the treatment of triple-negative breast cancer. LPO: Lipid peroxides; LDHA: Lactate dehydrogenase A, figureFileSmall=daDu2+YAbSNgQ4+mxwQ7mw==, figureFileBig=U6XFCr3FIcjH3Ig/+Ja94w==, tableContent=null), ArticleFig(id=1308498058170696312, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, language=EN, label=null, caption=null, figureFileSmall=kVtZgUpT2Q5hrdT51yXNHA==, figureFileBig=53qpFuggvgzUltwa6n7wlg==, tableContent=null), ArticleFig(id=1308498058300719737, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, language=CN, label=Fig.2, caption=The preparation process of SGF. PVP: Polyvinylpyrrolidone; SRF: Sorafenib; GF: Galloflavin, figureFileSmall=kVtZgUpT2Q5hrdT51yXNHA==, figureFileBig=53qpFuggvgzUltwa6n7wlg==, tableContent=null), ArticleFig(id=1308498058355245690, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, language=EN, label=null, caption=null, figureFileSmall=cXrx1MWGHaxrLxrzq2TrLw==, figureFileBig=Z5WVQ5jhWDbJO6N5OTPZOA==, tableContent=null), ArticleFig(id=1308498058418160251, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, language=CN, label=Fig.3, caption=Preparation and characterization of GF. A: The synthetic route of GF; B: 1H NMR spectrum of GF in DMSO-d6; C: Mass spectrometry of GF; D: UV spectra of GF and reactant GA. GA: Gallic acid, figureFileSmall=cXrx1MWGHaxrLxrzq2TrLw==, figureFileBig=Z5WVQ5jhWDbJO6N5OTPZOA==, tableContent=null), ArticleFig(id=1308498058476880508, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, language=EN, label=null, caption=null, figureFileSmall=eI4utBcCTiwT/SbsysRsaQ==, figureFileBig=ZBD8z8c0jDhVquo8FrrFBA==, tableContent=null), ArticleFig(id=1308498058535600765, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, language=CN, label=Fig.4, caption=Characterization of SGF. A: Dynamic light scattering (DLS) analysis of SGF; B: Transmission electron microscope (TEM) image of SGF. Scale bar = 100 nm; C: Zeta potential of SGF, figureFileSmall=eI4utBcCTiwT/SbsysRsaQ==, figureFileBig=ZBD8z8c0jDhVquo8FrrFBA==, tableContent=null), ArticleFig(id=1308498058770481790, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, language=EN, label=null, caption=null, figureFileSmall=SwHbpw23hXxStGdmy6WHMQ==, figureFileBig=YZt1QYx8gw79jKI7mnJW+g==, tableContent=null), ArticleFig(id=1308498058850173567, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, language=CN, label=Fig.5, caption=Characterization of SGF. A: Stability of SGF nanosystem in different media (n = 3, $ \overline{x} $ ± s); B: UV-vis spectra of SGF and reactants; C: UV-vis spectra of MB, MB after reaction with H2O2 (100 μmol·L-1), and MB treated with H2O2 (100 μmol·L-1) in the presence of SGF under pH 6.5. DMEM: Dulbecco's modified eagle medium; UV-vis: Ultraviolet-visible spectrophotometry; MB: Methylene blue, figureFileSmall=SwHbpw23hXxStGdmy6WHMQ==, figureFileBig=YZt1QYx8gw79jKI7mnJW+g==, tableContent=null), ArticleFig(id=1308498058921476736, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, language=EN, label=null, caption=null, figureFileSmall=TaBMw52b/bNPFT6IrYqizw==, figureFileBig=O2PRGbRvJA/MAIlsQ53LFA==, tableContent=null), ArticleFig(id=1308498059001168513, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, language=CN, label=Fig.6, caption=Photothermal properties of the SGF nanosystem. A: Temperature elevation curves of the SGF nanosystem under laser irradiation (n = 3, $ \overline{x} $ ± s); B: Photothermal stability assessment of the SGF nanosystem over multiple heating-cooling cycles, figureFileSmall=TaBMw52b/bNPFT6IrYqizw==, figureFileBig=O2PRGbRvJA/MAIlsQ53LFA==, tableContent=null), ArticleFig(id=1308498059080860290, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, language=EN, label=null, caption=null, figureFileSmall=4GvuNQr77Otn5R35ovk8WQ==, figureFileBig=XiIhT1JLwc9r6QoF0tWypQ==, tableContent=null), ArticleFig(id=1308498059156357763, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, language=CN, label=Fig.7, caption=Cytotoxicity of the SGF nanosystem. A: CI isobologram analysis of SRF and GF; B: Dark toxicity of various preparations on 4T1 cells; C: In vitro cytotoxicity of different formulations against 4T1 cells with or without 808 nm laser irradiation. CI: Combination index. n = 3, $ \overline{x} $ ± s. *P < 0.05, **P < 0.01, ***P < 0.001. ns: Not significant, figureFileSmall=4GvuNQr77Otn5R35ovk8WQ==, figureFileBig=XiIhT1JLwc9r6QoF0tWypQ==, tableContent=null), ArticleFig(id=1308498059240243844, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, language=EN, label=null, caption=null, figureFileSmall=g4Dp2nOCGfUQsjq3ROs3nQ==, figureFileBig=EaEqtMPgOjHgbpTNYghtxg==, tableContent=null), ArticleFig(id=1308498060913771141, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, language=CN, label=Fig.8, caption=Mechanistic investigation of the SGF nanosystem. A: ROS levels in 4T1 cells after receiving different treatments. Scale bar = 100 µm; B: Cell morphology of 4T1 cells after different treatments. Scale bar = 100 µm; C: Mean fluorescence intensity of lipid peroxides detected by Liperfluo; D: Intracellular lactate levels in each group. ROS: Reactive oxygen species. n = 3, $ \overline{x} $ ± s. *P < 0.05, ***P < 0.001. ns: Not significant, figureFileSmall=g4Dp2nOCGfUQsjq3ROs3nQ==, figureFileBig=EaEqtMPgOjHgbpTNYghtxg==, tableContent=null), ArticleFig(id=1308498060985074310, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
SRF:GFDiameter/nmPDIBaseline
1:0.2162.71 ± 2.240.137 ± 0.0658.9 ± 0.8
1:0.5141.10 ± 2.290.186 ± 0.0277.3 ± 1.1
1:1136.20 ± 0.830.103 ± 0.0129.2 ± 0.7
1:2158.01 ± 4.450.313 ± 0.0235.4 ± 1.4
1:5189.42 ± 6.750.194 ± 0.8656.3 ± 0.3
), ArticleFig(id=1308498061068960391, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, language=CN, label=Tab.1, caption=

Characterization of SGF nanoparticles with different feed ratios. PDI: Polydispersity index. n = 3, $ \overline{x} $ ± s

, figureFileSmall=null, figureFileBig=null, tableContent=
SRF:GFDiameter/nmPDIBaseline
1:0.2162.71 ± 2.240.137 ± 0.0658.9 ± 0.8
1:0.5141.10 ± 2.290.186 ± 0.0277.3 ± 1.1
1:1136.20 ± 0.830.103 ± 0.0129.2 ± 0.7
1:2158.01 ± 4.450.313 ± 0.0235.4 ± 1.4
1:5189.42 ± 6.750.194 ± 0.8656.3 ± 0.3
), ArticleFig(id=1308498061148652168, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
SRF:GFDEE/%DLE/%
SRFGFSRFGF
1:0.515.38 ± 3.2913.38 ± 0.593.10 ± 0.433.42 ± 1.65
1:118.99 ± 1.3718.50 ± 0.063.18 ± 0.223.86 ± 1.10
1:216.23 ± 2.2511.53 ± 0.443.14 ± 0.043.58 ± 0.96
), ArticleFig(id=1308498061228343945, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, language=CN, label=Tab.2, caption=

Encapsulation efficiency and drug loading of SGF with different feed ratios. DEE: Drug encapsulation efficiency; DLE: Drug loading efficiency. n = 3, $ \overline{x} $ ± s

, figureFileSmall=null, figureFileBig=null, tableContent=
SRF:GFDEE/%DLE/%
SRFGFSRFGF
1:0.515.38 ± 3.2913.38 ± 0.593.10 ± 0.433.42 ± 1.65
1:118.99 ± 1.3718.50 ± 0.063.18 ± 0.223.86 ± 1.10
1:216.23 ± 2.2511.53 ± 0.443.14 ± 0.043.58 ± 0.96
)], attaches=null, journal=Journal(id=1189982048455397383, delFlag=0, nameCn=药学学报, nameEn=Acta Pharmaceutica Sinica, nameHistory1=null, nameHistory2=null, issn=0513-4870, eissn=null, cn=11-2163/R, coden=null, periodic=0, language=CN, oaType=null, ccby=null, superviseOffice=null, ownerOffice=null, pubOffice=null, editorOffice=null, officeType=null, aims=null, clcCode=null, officeProv=null, officeCity=null, officeAddr=null, officeZip=null, officeEmail=null, officePhone=null, editDirector=null, officeDirector=null, officeDirectorPhone=null, officeStaffNum=null, officeEmpNum=null, coverPicUrl=BTxjudbJDVO4PqdBR6On6Q==, journalPrice=null, startedYear=null, abbrevIsoEn=null, journalRemark=null, publicationField=null, createdTime=1761643429151, updatedTime=1788948913902, createdBy=18614031015, updatedBy=13041195026, firstLetterCn=Y, firstLetterEn=Y, subjectCode=Medical and Pharmaceutical Sciences, subjectName=null, subjectCodeEn=Medical and Pharmaceutical Sciences, subjectNameEn=null, picCn=BTxjudbJDVO4PqdBR6On6Q==, picEn=c4l1ckL55nWbhl1KrFdWIA==, jcr=null, cjcr=null, exts=[JournalExt(id=1304509553505227679, language=CN, name=药学学报, nameHistory1=null, nameHistory2=null, managedBy=中国科学技术协会, sponsoredBy=中国药学会、中国医学科学院药物研究所, publishedBy=《药学学报》编辑委员会编辑出版, editorOffice=, officeProv=null, officeCity=null, officeAddr=, officeZip=, editDirector=, officeDirector=null, officePhone=null, coverPicUrl=null, journalRemark=, submitArticleUrl=null, websiteUrl=, createdTime=1788948914171, updatedTime=1788948914171, createdBy=13041195026, updatedBy=13041195026, submissionGuidelinesUrl=, submissionAuthorUrl=https://www.yxxb.com.cn/journalx_yxxb/authorLogOn.action, submissionEditorUrl=https://www.yxxb.com.cn/journalx_yxxb/editorLogOn.action, submissionReviewUrl=https://www.yxxb.com.cn/journalx_yxxb/expertLogOn.action, submissionCeEditorUrl=, submissionAeEditorUrl=, option={"copyright":""}), JournalExt(id=1304509553559753632, language=EN, name=Acta Pharmaceutica Sinica, nameHistory1=null, nameHistory2=null, managedBy=, sponsoredBy=, publishedBy=, editorOffice=, officeProv=null, officeCity=null, officeAddr=, officeZip=, editDirector=, officeDirector=null, officePhone=null, coverPicUrl=null, journalRemark=, submitArticleUrl=null, websiteUrl=, createdTime=1788948914184, updatedTime=1788948914184, createdBy=13041195026, updatedBy=13041195026, submissionGuidelinesUrl=, submissionAuthorUrl=https://www.yxxb.com.cn/journalx_yxxb/authorLogOn.action, submissionEditorUrl=https://www.yxxb.com.cn/journalx_yxxb/editorLogOn.action, submissionReviewUrl=https://www.yxxb.com.cn/journalx_yxxb/expertLogOn.action, submissionCeEditorUrl=, submissionAeEditorUrl=, option={"copyright":""})], databaseList=null, tenantJournalId=1189982191388893191, websiteList=[Website(id=1189982271588340489, webName=null, webTitle=null, webDomain=null, webCopyrigh=null, webIpcNo=null, seoTitle=null, seoKeywords=null, seoDescription=null, tenantJournalId=null, journalId=1189982191388893191, journalNameCn=null, journalNameEn=null, grayFlag=null, tenantId=1146029695717560320, platformId=null, journalGroupId=null, journalGroupNameCn=null, journalGroupNameEn=null, type=1, domain=https://castjournals.cast.org.cn/joweb/yxxb/CN, language=CN, createTime=1761643482348, createBy=18614031015, updateTime=1761643498101, updateBy=18614031015, name=药学学报-中文, tplId=1146099689490845704, title=药学学报, delFlag=0, indexPage=/home, props=[WebsiteProps(id=1189982873114448678, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271588340489, code=articleTextType, value=kx, createTime=1761643625763, updateTime=1761643625763, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982873093477155, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271588340489, code=banner, value=null, createTime=1761643625758, updateTime=1761643625758, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982873135420201, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271588340489, code=grayFlag, value=0, createTime=1761643625768, updateTime=1761643625768, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982873085088546, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271588340489, code=logo, value=https://castjournals.cast.org.cn/joweb/yxxb/CN/file/pic?fileId=w+t2v8bJnX5lh3+hRRJcDA==, createTime=1761643625756, updateTime=1761643625756, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982873152197419, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271588340489, code=minRunFlag, value=0, createTime=1761643625772, updateTime=1761643625772, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982873110254373, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271588340489, code=picServerUrl, value=https://castjournals.cast.org.cn/joweb/yxxb/CN/file/pic, createTime=1761643625762, updateTime=1761643625762, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982873143808810, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271588340489, code=silenceFlag, value=0, createTime=1761643625770, updateTime=1761643625770, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982873101865764, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271588340489, code=staticResourcePath, value=https://castjournals.cast.org.cn/joweb/cast_kjdb_cn_619/, createTime=1761643625760, updateTime=1761643625760, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982873122837287, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271588340489, code=themeColor, value=null, createTime=1761643625765, updateTime=1761643625765, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982873127031592, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271588340489, code=themeStyle, value=null, createTime=1761643625766, updateTime=1761643625766, creator=18614031015, updator=18614031015)]), Website(id=1189982271655449355, webName=null, webTitle=null, webDomain=null, webCopyrigh=null, webIpcNo=null, seoTitle=null, seoKeywords=null, seoDescription=null, tenantJournalId=null, journalId=1189982191388893191, journalNameCn=null, journalNameEn=null, grayFlag=null, tenantId=1146029695717560320, platformId=null, journalGroupId=null, journalGroupNameCn=null, journalGroupNameEn=null, type=1, domain=https://castjournals.cast.org.cn/joweb/yxxb/EN, language=EN, createTime=1761643482364, createBy=18614031015, updateTime=1761643514085, updateBy=18614031015, name=药学学报-英文, tplId=1146101810881728533, title=Acta Pharmaceutica Sinica, delFlag=0, indexPage=/home, props=[WebsiteProps(id=1189982903015633534, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271655449355, code=articleTextType, value=kx, createTime=1761643632892, updateTime=1761643632892, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982902990467707, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271655449355, code=banner, value=null, createTime=1761643632886, updateTime=1761643632886, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982903036605057, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271655449355, code=grayFlag, value=0, createTime=1761643632897, updateTime=1761643632897, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982902982079098, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271655449355, code=logo, value=https://castjournals.cast.org.cn/joweb/yxxb/EN/file/pic?fileId=w+t2v8bJnX5lh3+hRRJcDA==, createTime=1761643632884, updateTime=1761643632884, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982903053382275, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271655449355, code=minRunFlag, value=0, createTime=1761643632901, updateTime=1761643632901, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982903007244925, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271655449355, code=picServerUrl, value=https://castjournals.cast.org.cn/joweb/yxxb/EN/file/pic, createTime=1761643632890, updateTime=1761643632890, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982903044993666, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271655449355, code=silenceFlag, value=0, createTime=1761643632899, updateTime=1761643632899, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982902998856316, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271655449355, code=staticResourcePath, value=https://castjournals.cast.org.cn/joweb/cast_kjdb_en_623/, createTime=1761643632888, updateTime=1761643632888, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982903019827839, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271655449355, code=themeColor, value=null, createTime=1761643632893, updateTime=1761643632893, creator=18614031015, updator=18614031015), WebsiteProps(id=1189982903028216448, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189982271655449355, code=themeStyle, value=null, createTime=1761643632895, updateTime=1761643632895, creator=18614031015, updator=18614031015)])], journalTitle=药学学报, weixinUrl=null, journalUrl=https://www.yxxb.com.cn/aps, iacademicId=null, status=1, seqNo=null, journalTitleEn=Acta Pharmaceutica Sinica, journalPhotoCn=BTxjudbJDVO4PqdBR6On6Q==, journalPhotoEn=c4l1ckL55nWbhl1KrFdWIA==, journalFirstLetter=Y, journalRecommend=null, journalNew=null, journalCollection=null, jcrJf=null, cjcrJf=null, jcrJfStr=null, cjcrJfStr=null, submissionFirstDecision=null, sciSubjectClassification=null, casSubjectClassification=null, citeScore=null, totalCitationFrequency=null, icpCode=null, psCode=null, advertisingLicenseCode=null, copyrightInformation=null, country=null, option=, provinceCode=null, provinceName=null, collectFlag=false, interPubPlatform=, interPubPlatformUrl=null), detailUrlCn=https://castjournals.cast.org.cn/joweb/yxxb/CN/10.16438/j.0513-4870.2025-0697, detailUrlEn=https://castjournals.cast.org.cn/joweb/yxxb/EN/10.16438/j.0513-4870.2025-0697, pdfUrlCn=https://castjournals.cast.org.cn/joweb/yxxb/CN/PDF/10.16438/j.0513-4870.2025-0697, pdfUrlEn=https://castjournals.cast.org.cn/joweb/yxxb/EN/PDF/10.16438/j.0513-4870.2025-0697, aliStartDate=0, aliEndDate=0, collectionFlag=false, citedCount=null, citedUrl=null, previewStatus=0, delFlag=0, hasFullText=1, orderTime=1760198400000, fullTextJson=null, articleText=null, reference=null)
收藏切换
铁-没食子黄素自组装平台三重协同机制在三阴性乳腺癌治疗中的应用
收藏切换
PDF下载
余海晴 , 周天娇 , 王琰 , 车昊滨 , 茹佳雯 , 姜虎林 *
药学学报 | 研究论文 2025,60(10): 3229-3237
收起
收藏切换
药学学报 |研究论文 2025 , 60 (10) : 3229 -3237
铁-没食子黄素自组装平台三重协同机制在三阴性乳腺癌治疗中的应用
全屏
[Author(id=1308498054173524559, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, orderNo=0, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1308498054249022033, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, authorId=1308498054173524559, language=EN, stringName=Hai-qing YU, firstName=Hai-qing, middleName=null, lastName=YU, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1308498054328713810, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, authorId=1308498054173524559, language=CN, stringName=余海晴, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=中国药科大学药学院, 江苏 南京 210009, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1308498054077055563, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, xref=null, ext=[AuthorCompanyExt(id=1308498054089638476, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, companyId=1308498054077055563, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China), AuthorCompanyExt(id=1308498054102221389, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, companyId=1308498054077055563, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=中国药科大学药学院, 江苏 南京 210009)])]), Author(id=1308498054404211284, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, orderNo=1, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1308498054479708758, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, authorId=1308498054404211284, language=EN, stringName=Tian-jiao ZHOU, firstName=Tian-jiao, middleName=null, lastName=ZHOU, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1308498054555206231, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, authorId=1308498054404211284, language=CN, stringName=周天娇, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=中国药科大学药学院, 江苏 南京 210009, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1308498054077055563, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, xref=null, ext=[AuthorCompanyExt(id=1308498054089638476, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, companyId=1308498054077055563, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China), AuthorCompanyExt(id=1308498054102221389, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, companyId=1308498054077055563, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=中国药科大学药学院, 江苏 南京 210009)])]), Author(id=1308498054626509401, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, orderNo=2, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1308498054706201179, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, authorId=1308498054626509401, language=EN, stringName=Yan WANG, firstName=Yan, middleName=null, lastName=WANG, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1308498056409088604, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, authorId=1308498054626509401, language=CN, stringName=王琰, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=中国药科大学药学院, 江苏 南京 210009, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1308498054077055563, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, xref=null, ext=[AuthorCompanyExt(id=1308498054089638476, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, companyId=1308498054077055563, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China), AuthorCompanyExt(id=1308498054102221389, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, companyId=1308498054077055563, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=中国药科大学药学院, 江苏 南京 210009)])]), Author(id=1308498056488780382, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, orderNo=3, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1308498056564277856, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, authorId=1308498056488780382, language=EN, stringName=Hao-bin CHE, firstName=Hao-bin, middleName=null, lastName=CHE, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1308498056643969633, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, authorId=1308498056488780382, language=CN, stringName=车昊滨, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=中国药科大学药学院, 江苏 南京 210009, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1308498054077055563, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, xref=null, ext=[AuthorCompanyExt(id=1308498054089638476, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, companyId=1308498054077055563, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China), AuthorCompanyExt(id=1308498054102221389, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, companyId=1308498054077055563, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=中国药科大学药学院, 江苏 南京 210009)])]), Author(id=1308498056715272803, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, orderNo=4, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1308498056807547493, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, authorId=1308498056715272803, language=EN, stringName=Jia-wen RU, firstName=Jia-wen, middleName=null, lastName=RU, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1308498056866267750, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, authorId=1308498056715272803, language=CN, stringName=茹佳雯, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=中国药科大学药学院, 江苏 南京 210009, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1308498054077055563, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, xref=null, ext=[AuthorCompanyExt(id=1308498054089638476, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, companyId=1308498054077055563, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China), AuthorCompanyExt(id=1308498054102221389, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, companyId=1308498054077055563, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=中国药科大学药学院, 江苏 南京 210009)])]), Author(id=1308498056929182312, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, orderNo=5, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=jianghulin3@163.com, emailSecond=null, emailThird=null, correspondingAuthor=1, authorType=1, ext={EN=AuthorExt(id=1308498057000485482, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, authorId=1308498056929182312, language=EN, stringName=Hu-lin JIANG, firstName=Hu-lin, middleName=null, lastName=JIANG, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=*, address=School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1308498057067594347, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, authorId=1308498056929182312, language=CN, stringName=姜虎林, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=*, address=中国药科大学药学院, 江苏 南京 210009, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1308498054077055563, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, xref=null, ext=[AuthorCompanyExt(id=1308498054089638476, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, companyId=1308498054077055563, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China), AuthorCompanyExt(id=1308498054102221389, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308467769691894227, companyId=1308498054077055563, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=中国药科大学药学院, 江苏 南京 210009)])])]
余海晴, 周天娇, 王琰, 车昊滨, 茹佳雯, 姜虎林*
作者信息
  • 中国药科大学药学院, 江苏 南京 210009
通讯作者:
姜虎林, E-mail:
作者简介:

作者贡献:

余海晴承担了主要实验工作, 并撰写论文初稿; 周天娇负责研究设计, 稿件审阅与修改; 王琰参与了实验操作、数据整理和论文修改; 车昊滨和茹佳雯参与了实验操作与数据整理; 姜虎林为本研究的通讯作者, 统筹课题执行, 并对论文进行全面修改与定稿。所有作者均阅读并同意最终稿内容。

Iron-galloflavin self-assembled platform with triple synergistic mechanisms for the treatment of triple-negative breast cancer
Hai-qing YU, Tian-jiao ZHOU, Yan WANG, Hao-bin CHE, Jia-wen RU, Hu-lin JIANG*
Affiliations
  • School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China
出版时间: 2025-10-12 doi: 10.16438/j.0513-4870.2025-0697
文章导航
收藏切换
摘要
收起

三阴性乳腺癌侵袭性强、复发转移风险高且预后较差, 其中肿瘤细胞糖酵解导致的乳酸堆积是驱动三阴性乳腺癌恶性进展的关键因素。本研究据此构建了一种调控乳酸代谢的铁-没食子黄素自组装脂质过氧化加速器(self-assembled galloflavin-Fe lipid peroxidation accelerator, SGF) 用于抑制三阴性乳腺癌的生长。该体系由铁离子和没食子黄素酚羟基配位形成金属多酚网络装载药物索拉非尼制备得到。通过调整索拉非尼与没食子黄素的投料比为1:1, 制备得到粒径为136.20 ± 0.83 nm, 多分散系数为0.103 ± 0.012的SGF纳米粒, 实现双药协同装载。SGF的金属-多酚网络具有光热转换性能, 在808 nm光照射下可产生局部高热, 有效杀伤肿瘤细胞。在肿瘤微环境和溶酶体低pH条件下, 铁离子和没食子黄素解离释放药物索拉非尼, 借助铁离子补充和谷胱甘肽下调加速芬顿反应进行, 协同促进肿瘤细胞脂质过氧化进程; 没食子黄素通过抑制乳酸脱氢酶A, 下调丙酮酸向乳酸的转化, 减少乳酸生成, 从而改善肿瘤组织酸性微环境, 高效抑制三阴性乳腺癌的进展。本课题设计并构建的SGF纳米平台集光热效应、脂质过氧化诱导及乳酸代谢调控三重机制, 实现对三阴性乳腺癌及其高乳酸微环境的协同精准打击, 旨在为改善此类高度侵袭性乳腺癌的临床预后提供新的治疗策略。

三阴性乳腺癌  /  索拉非尼  /  没食子黄素  /  金属多酚网络  /  脂质过氧化

Triple-negative breast cancer (TNBC) is characterized by high invasiveness, a high risk of recurrence and metastasis, and poor prognosis. The accumulation of lactate in the tumor microenvironment produced by tumor cell glycolysis is a key factor driving the malignant progression of TNBC. In this study, we developed a lactate metabolism-regulating self-assembled galloflavin-Fe lipid peroxidation accelerator (SGF) to inhibit the growth of TNBC. The system was constructed by coordinating iron ions with the hydroxyl groups of galloflavin to form a metal-polyphenol network, which encapsulates the drug sorafenib. By adjusting the drug loading ratio of sorafenib to galloflavin at 1:1, SGF nanoparticles with a size of 136.20 ± 0.83 nm and a polydispersity index of 0.103 ± 0.012 were prepared, achieving efficient co-loading of both drugs. The metal-polyphenol network of SGF exhibits photothermal conversion properties, generating localized heat under 808 nm laser irradiation, effectively killing tumor cells. Under the low pH conditions of the tumor microenvironment and lysosomes, iron ions and galloflavin dissociate to release sorafenib, accelerating the Fenton reaction through iron ion supplementation and glutathione downregulation, which cooperatively promotes lipid peroxidation in tumor cells. Furthermore, galloflavin inhibits lactate dehydrogenase A, downregulating the conversion of pyruvate to lactate and reducing lactate production, thereby improving the acidic tumor microenvironment and efficiently suppressing the progression of TNBC. The SGF nanosystem designed and constructed in this study integrates three synergistic mechanisms-photothermal effect, lipid peroxidation induction, and lactate metabolism regulation to provide a synergistic and precise strike against TNBC and its high-lactate microenvironment, offering a new therapeutic strategy to improve the clinical prognosis of this highly invasive cancer.

triple-negative breast cancer  /  sorafenib  /  galloflavin  /  metal-polyphenol network  /  lipid peroxidation
余海晴, 周天娇, 王琰, 车昊滨, 茹佳雯, 姜虎林. 铁-没食子黄素自组装平台三重协同机制在三阴性乳腺癌治疗中的应用. 药学学报, 2025 , 60 (10) : 3229 -3237 . DOI: 10.16438/j.0513-4870.2025-0697
Hai-qing YU, Tian-jiao ZHOU, Yan WANG, Hao-bin CHE, Jia-wen RU, Hu-lin JIANG. Iron-galloflavin self-assembled platform with triple synergistic mechanisms for the treatment of triple-negative breast cancer[J]. Acta Pharmaceutica Sinica, 2025 , 60 (10) : 3229 -3237 . DOI: 10.16438/j.0513-4870.2025-0697
正文
收起
恶性肿瘤是全球主要健康威胁之一。肿瘤细胞的无限增殖性、高复发转移风险和耐药性是导致肿瘤患者死亡的主要原因[1, 2]。在全球女性新发恶性肿瘤中, 乳腺癌的发病率位居第一[3]。与其他亚型相比, 三阴性乳腺癌(triple-negative breast cancer, TNBC) 因缺乏雌激素受体(estrogen receptor, ER)、孕激素受体(progesterone receptor, PR) 和人表皮生长因子受体2 (human epidermal growth factor receptor 2, HER-2) 表达[4], 对特异性内分泌疗法和靶向疗法不敏感[5], 治疗手段显著受限。目前, 手术与化疗仍是TNBC的主要临床治疗手段。然而, 常规术后辅助化疗疗效有限, 且TNBC细胞具有高度异质性且适应性强, 能够通过多种机制逃避免疫清除并产生耐药性, 大大降低了治疗效果, 最终导致肿瘤复发转移。
Warburg效应是肿瘤细胞区别于正常细胞的关键代谢特征, 表现为在氧气充足条件下仍优先通过糖酵解途径而非线粒体氧化磷酸化获取能量[6]。在肿瘤细胞内, 乳酸脱氢酶A (lactate dehydrogenase A, LDHA) 催化丙酮酸还原为乳酸。随后, 大量乳酸通过主动转运机制被泵出细胞, 导致细胞外乳酸大量积累[7-9]。这种代谢重编程虽在能量效率上低于氧化磷酸化, 却为肿瘤恶性进展提供了多重优势。乳酸作为糖酵解的关键终产物, 在肿瘤微环境(tumor microenvironment, TME) 中具有活跃的生物学功能, 不仅表现出抗氧化作用, 也能够通过增强细胞耐药、上调血管生成、诱导细胞免疫逃逸为肿瘤细胞的侵袭和远处转移创造条件[10], 增强肿瘤细胞迁移倾向。
化学动力学治疗(chemodynamic therapy, CDT) 是一种基于TME特点的靶向治疗策略。其核心机制是借助芬顿反应或类芬顿反应催化肿瘤内源性过氧化氢(H2O2) 分解, 产生羟基自由基(·OH), 引发脂质过氧化链式反应[11]。·OH通过氧化损伤细胞内的关键生物大分子, 引发脂质过氧化、蛋白失活及DNA损伤, 最终诱导肿瘤细胞凋亡或坏死[12, 13]。与传统化疗和放疗相比, CDT的核心优势在于其肿瘤部位特异性和低全身毒性。然而, CDT的实际疗效常受限于TME的复杂性。TME中内源性H2O2和铁离子含量较低, 导致芬顿反应难以高效生成足够·OH[14]。此外, 乳酸及其相关代谢物本身具有一定的抗氧化能力, 可直接或间接地清除活性氧(reactive oxygen species, ROS), 中和其细胞毒性效应, 从而保护肿瘤细胞免受CDT的氧化损伤[15, 16]。因此, 有效降低肿瘤组织内的乳酸水平可解除其对CDT等多种治疗方式的抵抗性, 对提升抗肿瘤综合疗效及抑制转移潜能具有重要意义[17]。
近年来, 金属多酚网络(metal-phenolic networks, MPNs) 作为一类新兴光热材料, 因其绿色合成途径和优异的表面黏附能力而备受关注[18]。目前MPNs的构建主要依赖单宁酸(tannic acid, TA) 的多酚结构与多价金属离子螯合, 诱导TA实现快速自交联[19, 20]。通过文献查阅, 作者发现天然多酚化合物没食子黄素(galloflavin, GF) 因具有与TA相似的连苯三酚结构[21], 同样能够和铁离子配位自组装形成类似的MPNs[22, 23]。同时, GF已被证明是一种有效的LDHA抑制剂, 能够阻断丙酮酸向乳酸的转化, 显著降低TME酸化和乳酸积累[24], 有效逆转Warburg效应, 迫使肿瘤细胞从糖酵解代谢向氧化磷酸化途径转化[20]。因此, GF不仅是构建MPNs纳米载体的结构单元, 还能通过其固有的LDHA抑制活性主动干预肿瘤代谢, 形成“载体构建-代谢干预”的双功能协同机制。
基于上述金属离子-单宁酸组装体材料的启发及GF与TA的结构相似性, 本课题利用GF和Fe3+自组装形成MPNs, 并在其内部装载多激酶抑制剂索拉非尼(sorafenib, SRF), 构建铁-没食子黄素自组装脂质过氧化加速器(self-assembled galloflavin-Fe lipid peroxidation accelerator, SGF) (图1)。该平台通过多重协同机制发挥抗肿瘤作用: 首先, 负载的SRF通过抑制铁死亡防御通路增强细胞对铁死亡的敏感性[25]; 其次, 大量外源性Fe3+通过肿瘤细胞内还原性微环境转化为Fe2+ [26], 进而加速芬顿反应催化内源性H2O2生成具有细胞毒性的·OH攻击细胞内不饱和脂质或脂肪酸, 加速诱导铁死亡; 此外, GF通过抑制LDHA活性, 能够有效阻断丙酮酸向乳酸的转化从而显著降低TME中的乳酸水平, 并削弱细胞对治疗的抵抗作用。同时, 基于MPNs纳米平台的光热转换性能, SGF在808 nm近红外光照射下可产生局部高热效应, 直接杀伤肿瘤细胞并破坏肿瘤组织, 协同增强整体抗肿瘤疗效。这种多重调控机制SGF体系在递送药物的同时, 可持续性地重塑肿瘤能量代谢稳态, 为TNBC的联合治疗提供了新的治疗策略。
材料与方法
收起
药品与试剂  小鼠乳腺癌细胞4T1 (中国科学院上海保藏中心); 没食子酸(gallic acid, GA, L7A0X241, 上海阿拉丁生化科技股份有限公司); 氢氧化钾(江苏强盛功能化学股份有限公司); 盐酸(南京化学试剂股份有限公司); 四甲基偶氮唑蓝(南京凯基生物科技有限责任公司); 聚维酮K30 (安徽山河药用辅料股份有限公司); 三氯化铁(国药集团化学试剂有限公司); Liperfluo荧光探针(同仁化学科技有限公司); 乳酸检测试剂盒(亚科因生物技术有限公司); Dulbecco's Modified Eagle Medium (DMEM) 细胞培养基(南京凯基生物科技有限责任公司); 胎牛血清(兰州荣晔生物科技有限公司); DCFH-DA (0000187251, 西格玛奥德里奇上海贸易有限公司)。
仪器  梅特勒分析天平(XS 105, 瑞士梅特勒-托利多公司); 超声波清洗机(HT 7700, 苏州欧亚超声设备有限公司); 多功能酶标仪(MultiskanFC, 美国Thermo Scientific公司); 涡旋仪(MX-S)、磁力搅拌器(MS-H-S)、低温高速冷冻离心机(D3024R) (大龙兴创实验仪器有限公司); 超声细胞破碎仪(JY92-IIN, 南京先欧仪器制造有限公司); 808 nm激光器(MDL-L-H808, 长春新产业光电技术有限公司); 高效液相色谱仪(1260 Infinity Ⅱ, 美国安捷伦公司); 动态光散射激光粒度仪(NanoBrook Omni, 美国Brookhaven公司); Zeta电位分析仪(BeNano 90 Zeta, 丹东百特仪器股份有限公司); 透射电子显微镜(FEI Talos F200X G2, 赛默飞世尔科技公司); 色谱柱(XB-C18, 美国安捷伦公司); 倒置荧光显微镜(Leica DMi8, 徕卡显微系统上海贸易有限公司)。
GF的合成  取GA (1.00 g, 5.87 mmol) 置于烧杯中, 加入水/乙醇(1:1, v/v) 混合溶剂8.00 mL溶解。在持续搅拌下缓慢滴加5.00 mol·L-1氢氧化钾溶液(4.70 mL, 23.5 mmol), 反应体系在室温(25 ± 2 ℃), 持续流通空气条件下搅拌反应12 h。反应结束后抽滤收集析出的绿色钾盐沉淀, 将该盐转移至50 ℃水浴中, 加入5.00 mL去离子水重新溶解, 用2.00 mol·L-1盐酸溶液调节体系至pH 4.00进行酸化。析出的GF粗产物经布氏漏斗抽滤, 依次用无水乙醚(5 mL×3) 和二氯甲烷(5 mL×3) 分次洗涤, 最后通过真空干燥器(40 ℃/0.1 MPa) 干燥至恒重, 获得绿色结晶状目标产物[24]。
GF的表征  称取适量GA、GF使用DMSO-d6溶解, 使用核磁共振仪扫描1H NMR图谱; 通过紫外分光光度计于300~800 nm波长扫描紫外-可见分光光度法(ultraviolet-visible spectrophotometry, UV-vis) 图谱; 采用高分辨质谱仪进行电喷雾电离质谱分析, 采用正离子模式扫描(m/z 50~1 500)。
载药纳米粒的制备  SGF的制备如图2所示。首先, 将SRF溶液(50 μL, 10 mg·mL-1) 与GF溶液(250 μL, 2 mg·mL-1) 混合均匀, 制得溶液A; 随后, 称取聚乙烯吡咯烷酮(polyvinylpyrrolidone, PVP, 3.3 mg) 溶于超纯水(2 mL) 中, 并在剧烈搅拌下(约700 r·min-1) 将三氯化铁六水合物(FeCl3·6H2O) 水溶液(100 μL, 10 mg·mL-1) 逐滴滴加至PVP水溶液中, 持续快速搅拌10 min, 制得溶液B; 然后在冰水浴条件下, 将溶液B置于超声破碎仪中(功率设定为额定功率的10%, 脉冲模式: 工作3 s/间歇3 s), 在超声作用下将溶液A缓慢、匀速地逐滴滴加到持续剧烈搅拌的溶液B中, 整个滴加过程控制在5 min完成; 最终经离心(8 000 r·min-1、10 min) 后, 收集上清液, 即为目标SGF纳米复合物。
处方筛选  制备不同双药比例(SRF:GF = 1:0.2、1:0.5、1:1、1:2、1:5, m/m) 的SGF纳米粒, 采用动态光散射激光粒度仪同步测定流体力学直径(Z-average), 通过有机溶剂破坏法对SGF的包封率(drug encapsulation efficiency, DEE) 和载药量(drug loading efficiency, DLE) 进行检测。准确移取100 μL SGF纳米粒, 加入900 μL乙腈(色谱纯) 中涡旋混匀, 超声破碎30 min使载药纳米粒完全被破坏。然后用0.22 μm有机滤头过滤后进样分析。HPLC法测定262 nm处的色谱峰, 即得载药纳米粒内所包载的SRF (RT = 34.1 min) 和GF (RT = 7.5 min) 的总药量, 记为Wt, 根据公式(1) 和(2) 分别计算载药纳米粒的DEE和DLE:
$\operatorname{DEE}(\%)=W_{\mathrm{t}} / W_{\mathrm{d}} \times 100 \%$
$\operatorname{DLE}(\%)=W_{\mathrm{t}} /\left(W_{\mathrm{t}}+W_{\mathrm{p}}\right) \times 100 \% $
其中, Wt为纳米粒中所含药物的质量; Wd为药物的总投药量; Wp为纳米粒中载体的质量。
色谱条件  色谱柱: Agilent ZORBAX SB-C18; 流动相: 0.1%三氟乙酸水溶液(A相)-乙腈(B相); 梯度洗脱0~5 min, 5%~15% B; 5~15 min, 15%~30% B; 15~25 min, 30%~100% B; 25~30 min, 100% B; 30~40 min, 100%~5% B; 流速: 0.3 mL·min-1; 柱温: 30 ℃; 进样量: 10 µL。
形态考察  将SGF纳米混悬液用PBS缓冲液(10 mmol·L-1, pH 7.40) 按1:10 (v/v) 稀释。取适量液体滴在铜网上, 烘干后在铜网上滴加1%的磷钨酸溶液, 室温静置3~5 min进行染色, 待自然干燥后使用透射电子显微镜观察纳米粒的粒径大小和形态并进行拍照。
粒径考察  将SGF纳米混悬液用PBS缓冲液(10 mmol·L-1, pH 7.40) 按1:10 (v/v) 稀释后, 转移至检测皿中, 采用动态光散射激光粒度仪测定Z-average。每个样品平行测定3次, 取平均值。
电位考察  将SGF纳米混悬液用PBS缓冲液(10 mmol·L-1, pH 7.40) 按1:200 (v/v) 稀释后, 转移至zeta电位样品池内, 平衡后测量样品的电位。
稳定性考察  分别使用超纯水、PBS、0.9%氯化钠注射液、5%葡萄糖溶液及含有10% FBS的高糖DMEM培养基对SGF进行稀释, 取1 mL待检测液转移至比色皿中, 采用动态光散射法(dynamic light scattering, DLS) 测量其粒径, 连续检测7天。最后根据结果绘制粒径-时间变化曲线, 考察制剂的稳定性。
UV-vis表征  采用紫外-可见光谱法表征SGF纳米粒的药物包封效果, 具体操作流程如下: 取SGF纳米粒分散液50 μL, 加入950 μL乙腈溶剂, 经超声处理10 min后充分解离纳米结构并释放药物; 以纯乙腈为空白对照, 游离SRF、GF、FeCl3的乙腈溶液为单药参照, 使用多功能酶标仪进行200~800 nm全波长扫描; 通过分析SGF样品在药物特征吸收峰处的信号响应, 验证药物分子包载成功。
·OH的检测  采用亚甲基蓝(methylene blue, MB) 降解法对ROS生成情况进行检测。首先配制3组反应体系——对照组(2.0 mL 0.1 mmol·L-1 MB溶液)、氧化组(对照组溶液与2.0 mL 1.0 mmol·L-1 H2O2混合)、实验组(氧化组溶液补加1.0 mL SGF); 将3组体系置于25 ℃避光孵育10 min后, 使用紫外-可见分光光度计进行全波长扫描(400~800 nm), 所有操作均在弱光环境完成。
温度变化曲线  制备不同浓度的SGF水溶液置于西林瓶中, 采用808 nm近红外激光器对样品进行光照, 每个浓度组设置3个平行样本。光照过程中, 使用红外测温仪实时记录溶液温度, 以此绘制温度变化曲线。
光热稳定性考察  将一定浓度的SGF水溶液分装至西林瓶中, 采用808 nm近红外激光器进行间歇式辐照实验。每个辐照周期包含5 min激光照射, 随后关闭光源使溶液自然冷却至室温, 组成单个循环。上述过程重复执行4个循环, 实时记录溶液的温度变化曲线。
细胞培养及传代  使用含10%胎牛血清、1%青链霉素高糖DMEM培养基培养4T1细胞, 37 ℃、5% CO2恒温培养箱进行贴壁培养。1:5比例每两天传代培养, 待细胞生长状态良好且处于对数生长期时进行下一步实验操作。
细胞毒性实验  采用四甲基偶氮唑蓝(thiazolyl blue tetrazolium bromide, MTT) 法考察纳米粒对4T1细胞的抑制作用。在96孔板中接种4T1细胞(1×104 cells/well), 37 ℃培养24 h后, 分别加入质量浓度为0~3 μg·mL-1的SRF、GF、SRF+GF、SRF+GF+Fe3+及SGF, 继续培养24 h。然后使用100 μL含有1 mg·mL-1 MTT的DMEM溶液替换含药培养基, 避光培养4 h, 去除上清后, 每孔加入150 μL DMSO, 振荡5 min使底部紫色结晶溶解, 使用酶标仪在490 nm波长下测量吸光度值。每组设置3个复孔, 根据公式(3) 计算细胞存活率:
$ \text { Cell viability (%) }=\frac{A_{\text {sample }}}{A_{\text {control }}} \times 100 \%$
其中, Asample、Acontrol分别为样品组、空白对照组在490 nm处的吸光度值。为准确评估SGF的光热作用, 选用SRF为2 μg·mL-1的治疗质量浓度进行光照杀伤评价。按照上述实验操作接种并处理细胞, 给药6 h后换液, 使用808 nm近红外光照射孔板10 min。继续培养18 h后, 用100 μL含有1 mg·mL-1 MTT溶液的培养基继续避光培养4 h, 去除上层含有MTT培养基后, 每孔加入150 μL DMSO, 振荡5 min使紫色结晶溶解, 采用酶标仪在490 nm波长下测量吸光度值。
协同指数测定  将4T1细胞接种至96孔板(1×104 cells/well), 孵育24 h后分别加入一定浓度梯度的单药或联合药液; 24 h之后, 通过MTT法检测细胞存活率并计算Fa值(药物抑制率); 最后使用CompuSyn软件, 输入单药与联合组的剂量-效应数据, 自动生成协同指数(combination index, CI) 值, CI < 1、= 1或 > 1分别表示协同、相加或拮抗作用。
ROS水平检测  实验设置为control组、SRF组、GF组、SRF+GF组、SRF+GF+Fe3+组、SGF组和SGF (+) 7组。将4T1细胞接种于12孔板(1×105 cells/well) 培养24 h后, 加入不同终质量浓度的药物作用(其中SRF为2 μg·mL-1, GF为2 μg·mL-1)。孵育6 h后, 换用10 μmol·L-1 DCHF-DA避光培养30 min。吸除探针溶液, PBS洗3次, 换用新鲜培养基, 使用808 nm近红外光对SGF (+) 组进行10 min定点照射, 使用倒置荧光显微镜观察细胞形态, 并对细胞内DCFH-DA荧光进行检测。
细胞形态  将4T1细胞按照1×105 cells/well的密度接种于12孔板中, 培养过夜。待细胞密度达到80%左右, 加入不同终质量浓度的药物(其中SRF为2 μg·mL-1, GF为2 μg·mL-1)。细胞分组与前述细胞实验相同。孵育6 h后, 使用808 nm近红外光对SGF (+) 组进行10 min定点照射。继续孵育18 h之后, 在倒置显微镜下观察不同组别细胞形态。
脂质过氧化水平检测  将4T1细胞接种于黑色96孔板(5×103 cells/well), 37 ℃培养24 h后更换含不同药物的培养基继续处理6 h。用含10 μmol·L-1 Liperfluo探针的新鲜培养基避光孵育15 min (37 ℃、5% CO2), 随后使用808 nm近红外光进行10 min定点照射。停止反应后, 加入含1%蛋白酶抑制剂的RIPA裂解液裂解细胞15 min, 于荧光酶标仪检测特异性信号(激发波长488 nm, 发射波长525 nm), 并以未处理组作为基准计算相对脂质过氧化水平。
乳酸水平检测  将4T1细胞接种于12孔板(1×105 cells/well) 培养24 h后, 加入不同终质量浓度的药物作用(其中SRF为2 μg·mL-1, GF为2 μg·mL-1)。细胞分组及处理方法与前述细胞实验相同。细胞与不同药物组共同孵育6 h后, 用PBS洗涤细胞3次, 随后加入裂解液充分裂解细胞, 并于4 ℃以12 000 × g离心5 min。收集上清液按照乳酸检测试剂盒的操作说明检测细胞内乳酸含量。
数据分析  本研究使用SPSS统计软件(V.23, IBM SPSS Software, USA) 对数据进行统计分析, 结果以平均值±标准差($ \overline{x} $ ± s) 表示, 采用one-way ANOVA分析各组数据间的差异, P < 0.05时表示各组数据间的差异具有统计学意义。
结果
收起
1　GF的制备和表征
1.1　 1H NMR结果
GF的反应式如图3A所示。通过1H NMR光谱对合成产物进行结构表征(图3B), 在δH: 6.88和7.16处观测到特征性芳香质子信号峰, 与文献[24]报道一致, 证实了目标产物GF的成功合成。
1.2　质谱及UV-vis分析
如图3C所示, 质谱分析结果显示产物的特征离子峰: m/z = 279.16 [M+H]+、301.14 [M+Na]+、317.12 [M+K]+。其中[M+H]+峰(m/z = 279.16) 与GF质子化分子质量(理论值278.04 + 1.01) 高度吻合, 而[M+Na]+和[M+K]+加合峰进一步佐证了分子结构的准确性。UV-Vis进一步提供结构佐证(图3D), 原料GA仅在270 nm处存在单一吸收峰, 而合成产物GF在258、378及395 nm处呈现3个特征吸收峰, 与文献[24]报道的GF光谱数据一致。质谱与UV-Vis数据的相互印证, 证明了GF的成功制备。
2　载药纳米粒的表征
2.1　处方筛选
由表1、2可知, SRF与GF的质量比(m/m) 显著影响纳米粒粒径。当投料比在1:0.2至1:5范围内变化时, 粒径呈先减小后增大的趋势。在投料质量比为1:1时, 共载纳米粒展现出最优综合性能: 粒径分布窄且处于理想纳米尺度, 分散均一性显著提升, 同时包封率与载药量达最高值, 因此确定投料比1:1为最佳处方。
2.2　形态学考察
载药纳米粒的形态学特征如图4所示, SGF纳米粒为单分散性[多分散系数(polydispersity index, PDI) 为0.103 ± 0.012], 粒径大小约为136.2 ± 0.8 nm的类球形结构, zeta电位为-3.93 ± 0.14 mV。以上数据表明, SGF纳米粒具有良好的粒径均一性与分散性。
2.3　稳定性考察
为考察纳米粒的稳定性, 将SGF纳米颗粒用纯水、PBS、生理盐水、5%葡萄糖溶液及含有10%FBS的高糖DMEM这5种介质稀释, 通过DLS法连续7天监测其粒径变化。实验结果如图5A所示, 该纳米体系在不同介质中均能维持稳定的粒径分布, 未出现显著聚集或降解现象。
2.4　UV-vis分析
如图5B所示, UV-Vis显示SGF在277与400 nm处呈现特征吸收峰, 分别对应游离SRF的芳环吸收带(275~280 nm) 及GF的醌式结构特征吸收(395~405 nm), 证实SRF与GF被成功装载至纳米载体中。
2.5　芬顿反应诱导·OH生成的检测
采用MB降解实验评估SGF在模拟TME (pH 6.5, 100 μmol·L-1 H2O2) 中产生·OH的能力。如图5C所示, 100 μmol·L-1 H2O2本身对MB的光谱没有影响; 然而, 与SGF孵育后, MB的吸光度下降, 表明SGF纳米复合物能够在酸性TME下快速释放铁离子, 通过芬顿反应生成·OH, 进而降解MB。
3　光热性质考察
3.1　温度变化曲线
为了评估SGF的光热转换作用, 研究了其在近红外激光照射下的温度变化情况。如图6A所示, 在激光照射下, 含有SGF水溶液的温度呈现显著的浓度依赖性升高。在较高浓度的SGF溶液中, 经过5 min光照, 其温度即可迅速升高至43 ℃, 能够有效杀伤肿瘤细胞的治疗温度范围。这一显著的升温效果凸显了SGF作为光热转换剂的潜力。
3.2　光热稳定性考察
SGF表现出优异的光热稳定性, 经过多次连续的光照与自然冷却循环处理后, 其光热转换效率未出现明显衰减, 依然能够维持高效的升温能力(图6B)。这种良好的稳定性对于材料在实际治疗过程中的重复使用尤为关键, 有助于保障其治疗效果的一致性和可靠性。
4　细胞毒性考察
采用MTT法评估SGF纳米粒的体外细胞毒性及协同效应。图7A为不同CI的分析结果, 当SRF与GF的质量比为2:1、1:1、1:2和1:5时, CI值均小于1, 表明两药联用具有显著协同作用。结合载药量与包封率优化结果, 最终选定SRF:GF = 1:1为最佳比例用于后续研究。MTT细胞毒性实验结果表明, 在未进行近红外光照条件下, 单独的GF对细胞生长几乎无抑制作用, 而SGF纳米粒则表现出显著的细胞毒性, 其抑制细胞生长的效果明显优于其他对照组, 且细胞存活率随纳米粒浓度升高呈下降趋势(图7B)。在808 nm近红外光照条件下(图7C), SGF (+) 组的细胞毒性进一步增强, 表明SGF具有优异的光热转换能力。为了突出SGF在光照下的协同杀伤优势, 最终选取细胞存活率约为50%时对应的给药剂量作为后续实验的参考浓度: 即SRF和GF的质量浓度均为2 μg·mL-1。
5　体外机制考察
5.1　细胞内ROS水平检测
CDT借助芬顿反应通过上调细胞内ROS水平损伤细胞。本实验利用ROS特异性荧光探针DCFH-DA检测胞内的ROS水平。如图8A所示, 与control组相比, SRF、SRF+GF组细胞逐渐开始变圆、皱缩, 其中SRF+GF组细胞开始有绿色荧光表达。而SRF+GF+Fe3+组能够更显著增加细胞内ROS的含量, 说明Fe3+的引入能够借助芬顿反应增加‧OH生成, 同样的结果能够在SGF组中观察到。SGF (+) 组在接受光照后有更多死细胞产生, 显示出极好的光热杀伤作用。
5.2　细胞形态
延长给药时间后不同制剂组的细胞形态如图8B所示, GF对4T1细胞无显著毒性; SRF处理可观察到明显的细胞凋亡形态; 而SRF+GF、SRF+GF+Fe3+和SGF组则表现出更强的细胞毒性, 其中制剂组SGF能够显著增加细胞死亡率, 光照之后SGF (+) 组的细胞裂解为碎片形式。
5.3　细胞内脂质过氧化水平检测
为了检测CDT产生的‧OH对不饱和脂质的氧化情况, 使用Liperfluo作为荧光探针。Liperfluo会被脂质过氧化物特异性氧化, 在485 nm激发条件下发出绿色荧光信号。如图8C所示, 与control组相比, SRF、GF和SRF+GF组没有明显的信号上升。SRF作为酪氨酸激酶抑制剂, 通过抑制System Xc-降低细胞内谷胱甘肽(glutathione, GSH) 水平, 削弱细胞的抗氧化防御能力; GF能够通过抑制LDHA活性, 下调乳酸生成量, 然而SRF、GF和SRF+GF组均未观察到显著的脂质过氧化积累。对比之下, SGF+GF+Fe3+组和SGF组的荧光强度显著增强, 表明其细胞内脂质过氧化产物水平显著升高。这归因于其组成中的Fe3+可在细胞内经GSH, NADPH及抗坏血酸等还原性物质还原为Fe2+, 进而加速芬顿反应, 高效催化ROS生成, 进一步加剧脂质过氧化。此外, 在施加808 nm近红外光照条件下, SGF (+) 组的脂质过氧化物水平进一步显著升高, 这可能是因为光热转换产生的局部升温不仅可直接损伤细胞, 也能够显著提升Fe3+/Fe2+转化效率, 从而诱导脂质过氧化物的过量积累。
5.4　乳酸水平检测
细胞内乳酸代谢水平结果如图8D所示, 与对照组相比, SRF组乳酸水平有所上升, 这可能是因为SRF抑制了线粒体氧化磷酸化, 从而增加了乳酸的生成[27]。另一方面, GF作为LDHA的抑制剂, 能够显著降低细胞内乳酸含量。这一结果表明GF能够有效阻断糖酵解途径中乳酸的生成, 并通过抑制LDHA的活性减少乳酸积累。此外, GF的加入显著下调了SRF+GF组、SRF+GF+Fe3+组、SGF组和SGF (+) 组的乳酸含量, 这表明SGF纳米平台通过协同作用不仅能抑制乳酸的生成, 还有望改善肿瘤细胞的代谢状态。
6　讨论
TNBC具有高侵袭性、高复发转移风险和不良预后等特点。肿瘤细胞通过糖酵解途径生成的过量乳酸在微环境中的积累被认为是驱动不良预后的关键因素。为应对这一挑战, 本研究构建了SGF纳米系统, 并通过实验验证该体系通过增强氧化应激、抑制乳酸生成, 提高对TNBC的杀伤效果。SGF纳米体系采用金属-多酚网络自组装的方式, 实现了双药高效负载和稳定包封, 表现出优异的稳定性。在近红外光照射下, SGF能够迅速达到肿瘤损伤所需的温度, 展现出优异的光热转换能力。细胞实验结果表明, SGF一方面可激活ROS级联反应, 诱导脂质过氧化物在细胞内爆发式积累, 有效触发铁死亡; 另一方面通过靶向抑制糖酵解关键酶, 显著降低乳酸生成, 有望缓解肿瘤相关免疫抑制微环境。综上, SGF通过光热转换、脂质过氧化诱导及乳酸代谢干预三重协同机制, 协同破坏肿瘤细胞的氧化还原稳态和代谢基础, 为TNBC的精准治疗提供了全新策略与潜力。

文献
收起
参考文献 引证文献
排序方式：
1
França GS, Baron M, King BR, et al. Cellular adaptation to cancer therapy along a resistance continuum [J]. Nature, 2024, 631: 876-883.
2
Klein CA. Selection and adaptation during metastatic cancer progression [J]. Nature, 2013, 501: 365-372.
3
Siegel RL, Kratzer TB, Giaquinto AN, et al. Cancer statistics, 2025 [J]. Ca Cancer J Clin, 2025, 75: 10-45.
4
Yin L, Duan JJ, Bian XW, et al. Triple-negative breast cancer molecular subtyping and treatment progress [J]. Breast Cancer Res, 2020, 22: 61.
5
Bianchini G, De Angelis C, Licata L, et al. Treatment landscape of triple-negative breast cancer-expanded options, evolving needs [J]. Nat Rev Clin Oncol, 2022, 19: 91-113.
6
Fendt SM. 100 years of the Warburg effect: a cancer metabolism endeavor [J]. Cell, 2024, 187: 3824-3828.
7
Swietach P, Boedtkjer E, Pedersen SF. How protons pave the way to aggressive cancers [J]. Nat Rev Cancer, 2023, 23: 825-841.
8
Liu XD, Li SJ, Cui QH, et al. Activation of GPR81 by lactate drives tumour-induced cachexia [J]. Nat Metab, 2024, 6: 708-723.
9
Wang N, Zhu MJ, Jiang YM, et al. Neutrophil-mediated tumor discrimination biomimetic nanodevice for precise tumor eradication and metastasis cascade perturbing [J]. ACS Appl Mater Interfaces, 2025, 17: 23680-23690.
10
Bohn T, Rapp S, Luther N, et al. Tumor immunoevasion via acidosis-dependent induction of regulatory tumor-associated macrophages [J]. Nat Immunol, 2018, 19: 1319-1329.
11
Zhao PR, Li HY, Bu WB. A forward vision for chemodynamic therapy: issues and opportunities [J]. Angew Chem Int Ed Engl, 2023, 62: e202210415.
12
Wu JY, Meng Y, Wu F, et al. Ultrasound-driven non-metallic fenton-active center construction for extensive chemodynamic therapy [J]. Adv Mater, 2024, 36: e2307980.
13
Xing Y, Xiu JD, Zhou MY, et al. Copper single-atom jellyfish-like nanomotors for enhanced tumor penetration and nanocatalytic therapy [J]. ACS Nano, 2023, 17: 6789-6799.
14
Zhou TJ, Xu Y, Xing L, et al. A harmless-harmful switchable and uninterrupted laccase-instructed killer for activatable chemodynamic therapy [J]. Adv Mater, 2021, 33: e2100114.
15
Michalek RD, Gerriets VA, Jacobs SR, et al. Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets [J]. J Immunol, 2011, 186: 3299-3303.
16
Hirschhaeuser F, Sattler UG, Mueller-Klieser W. Lactate: a metabolic key player in cancer [J]. Cancer Res, 2011, 71: 6921-6925.
17
Zhou TJ, Wan X, Zhang MM, et al. Tumor microenvironment-initiated lipid redox cycling for efficient triple-negative breast cancer therapy [J]. Biomaterials, 2023, 300: 122205.
18
Thompson KH, Orvig C. Boon and bane of metal ions in medicine [J]. Science, 2003, 300: 936-939.
19
Ejima H, Richardson JJ, Liang K, et al. One-step assembly of coordination complexes for versatile film and particle engineering [J]. Science, 2013, 341: 154-157.
20
Guo JL, Ping Y, Ejima H, et al. Engineering multifunctional capsules through the assembly of metal-phenolic networks [J]. Angew Chem Int Ed Engl, 2014, 53: 5546-5551.
21
Farabegoli F, Vettraino M, Manerba M, et al. Galloflavin, a new lactate dehydrogenase inhibitor, induces the death of human breast cancer cells with different glycolytic attitude by affecting distinct signaling pathways [J]. Eur J Pharm Sci, 2012, 47: 729-738.
22
Zhang Z, Li XN, Liu WQ, et al. Polyphenol nanocomplex modulates lactate metabolic reprogramming and elicits immune responses to enhance cancer therapeutic effect [J]. Drug Resist Updat, 2024, 73: 101060.
23
Zhou Y, Ke P, Bao XY, et al. Peptide nano-blanket impedes fibroblasts activation and subsequent formation of pre-metastatic niche [J]. Nat Commun, 2022, 13: 2906.
24
Manerba M, Vettraino M, Fiume L, et al. Galloflavin (CAS 568-80-9): a novel inhibitor of lactate dehydrogenase [J]. ChemMedChem, 2012, 7: 311-317.
25
Zhou TJ, Zhang MM, Liu DM, et al. Glutathione depletion and dihydroorotate dehydrogenase inhibition actuated ferroptosis-augment to surmount triple-negative breast cancer [J]. Biomaterials, 2024, 305: 122447.
26
He YJ, Liu XY, Xing L, et al. Fenton reaction-independent ferroptosis therapy via glutathione and iron redox couple sequentially triggered lipid peroxide generator [J]. Biomaterials, 2020, 241: 119911.
27
Fiume L, Manerba M, Vettraino M, et al. Effect of sorafenib on the energy metabolism of hepatocellular carcinoma cells [J]. Eur J Pharmacol, 2011, 670: 39-43.
2025年第60卷第10期
PDF下载
194
85
引用本文
BibTeX
文章信息
doi: 10.16438/j.0513-4870.2025-0697
  • 接收时间：2025-06-20
  • 首发时间：2026-09-20
  • 出版时间：2025-10-12
补充材料
相关文章
文章信息
作者
出版历史
  • 收稿日期：2025-06-20
  • 修回日期：2025-08-04
基金
作者信息
    中国药科大学药学院, 江苏 南京 210009

通讯作者:

姜虎林, E-mail:
参考文献
分享链接
https://castjournals.cast.org.cn/joweb/yxxb/CN/10.16438/j.0513-4870.2025-0697
分享至
全文二维码

扫描看全文

引用本文
BibTeX
本文的引用情况
2种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
关闭全屏
相关链接
论文
最新文章
热读文章
热点专题
内参
蓝皮书
产业发展报告
传播力报告
期刊分级目录
资讯
学术新闻
行业新闻
学术会议
行业会议
关于
关于我们
联系我们
北京市海淀区学院南路86号
100081
010-62662699（运营及技术支持）
qkjq@cast.org.cn

中国科学技术协会版权所有 京ICP 备10216604号-4 海淀分局备案 1101084647
科技导报社主办 中国科协信息中心技术支持