Article(id=1208402654896697783, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1208402647258870040, articleNumber=null, orderNo=null, doi=10.16438/j.0513-4870.2020-1572, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1601395200000, receivedDateStr=2020-09-30, revisedDate=1602691200000, revisedDateStr=2020-10-15, acceptedDate=null, acceptedDateStr=null, onlineDate=1766035243962, onlineDateStr=2025-12-18, pubDate=1618156800000, pubDateStr=2021-04-12, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1766035243962, onlineIssueDateStr=2025-12-18, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1766035243962, creator=13701087609, updateTime=1766035243962, updator=13701087609, issue=Issue{id=1208402647258870040, tenantId=1146029695717560320, journalId=1189982191388893191, year='2021', volume='56', issue='4', pageStart='895', pageEnd='1200', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1766035242142, creator=13701087609, updateTime=1766137207216, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1208830319826964817, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1208402647258870040, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1208830319826964818, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1208402647258870040, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=1016, endPage=1024, ext={EN=ArticleExt(id=1208402655307739592, articleId=1208402654896697783, tenantId=1146029695717560320, journalId=1189982191388893191, language=EN, title=Research progress in tumor microenvironmentally modulating nanostructures, columnId=1190335348648547107, journalTitle=Acta Pharmaceutica Sinica, columnName=Reviews, runingTitle=null, highlight=null, articleAbstract=
Tumor microenvironment (TME) is a complex comprehensive system composed of immune cells, inflammatory cells, tumor-associated fibroblasts, microvessels, and various cytokines and chemokines. As the living environment of tumor cells, it's closely related to the occurrence, metastasis, and recurrence of tumors. The characteristics of tumor microenvironment include: weakly acidic environment, low oxygen, high concentration of reactive oxygen species (ROS) and reducing substances, immunosuppression, etc. A weakly acidic environment favors metastasis of tumor cells, hypoxia is conducive to the emergence of drug resistance, high concentration of ROS and reducing substances are beneficial for tumor treatment, and immunosuppressiveness facilitates immune escape. With the rapid development of nanotechnology, more and more nanostructures have been reported to achieve tumor treatment by regulating the tumor microenvironment. This review summarizes recent advances in the nanostructures used to regulate tumor microenvironment through changing elements, including hydrogen-ion concentration (pH), the concentration of oxygen (O2) and reactive oxygen species, and the activity of immune cells. Moreover, research directions in the future are pointed out in this review.
, correspAuthors=Yan-min JU, authorNote=null, correspAuthorsNote=null, copyrightStatement=Copyright ©2021 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, authorCompany=null, fund=null, authors=null, authorsList=Cai-xia SUN, Yan-min JU, Jian-jun DAI), CN=ArticleExt(id=1208402656851243542, articleId=1208402654896697783, tenantId=1146029695717560320, journalId=1189982191388893191, language=CN, title=肿瘤微环境调节型纳米材料的研究进展, columnId=1190335349655180086, journalTitle=药学学报, columnName=综述, runingTitle=null, highlight=null, articleAbstract=
肿瘤微环境（tumor microenvironment，TME）是由免疫细胞、炎症细胞、肿瘤相关成纤维细胞、微血管，以及各种细胞因子和趋化因子所构成的一个复杂的综合系统，作为肿瘤细胞的生存环境，它与肿瘤的发生、转移及复发密切相关。肿瘤微环境的特点包括：弱酸性环境、低氧、活性氧（reactive oxygen species，ROS）及还原性物质含量高、免疫抑制性等。弱酸性环境有利于肿瘤细胞的转移；低氧有利于耐药性的出现；ROS及还原性物质含量高有利于肿瘤的治疗；免疫抑制性有利于免疫逃逸的发生。随着纳米技术的不断发展，越来越多的纳米材料被报道可通过调节肿瘤微环境进而实现肿瘤治疗。本文主要综述了纳米材料在调节肿瘤微环境中的酸碱度（hydrogen-ion concentration，pH）、氧气（oxygen，O2）含量、ROS浓度及免疫细胞活性方面的最新研究进展，并对未来的研究方向做出了展望。
, correspAuthors=鞠艳敏, authorNote=null, correspAuthorsNote=
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10: 5108., articleTitle=An inhalable nanoparticulate STING agonist synergizes with radiotherapy to confer long-term control of lung metastases, refAbstract=null)], funds=[Fund(id=1208478679341056644, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1208402654896697783, awardId=2019YFC1605402, language=CN, fundingSource=国家重点研发资助项目(2019YFC1605402), fundOrder=null, country=null), Fund(id=1208478679471080082, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1208402654896697783, awardId=52002402, language=CN, fundingSource=国家自然科学基金青年科学基金资助项目(52002402), fundOrder=null, country=null), Fund(id=1208478679575937695, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1208402654896697783, awardId=null, language=CN, fundingSource=江苏省优势学科颠覆性计划, fundOrder=null, country=null)], companyList=[AuthorCompany(id=1208478673544528874, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1208402654896697783, xref=null, ext=[AuthorCompanyExt(id=1208478673552917482, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1208402654896697783, companyId=1208478673544528874, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1. School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China), AuthorCompanyExt(id=1208478673557111787, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1208402654896697783, companyId=1208478673544528874, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.中国药科大学生命科学与技术学院, 江苏 南京 211198)]), AuthorCompany(id=1208478673741660161, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1208402654896697783, xref=null, ext=[AuthorCompanyExt(id=1208478673750048770, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1208402654896697783, companyId=1208478673741660161, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2. School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China), AuthorCompanyExt(id=1208478673825546253, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1208402654896697783, companyId=1208478673741660161, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.中国药科大学药学院, 江苏 南京 211198)])], figs=[ArticleFig(id=1208478677017411969, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1208402654896697783, language=EN, label=null, caption=null, figureFileSmall=k3e2+Lp0ClutqmlHbjucMA==, figureFileBig=3BEq5iXU3yLizPmY41JPxQ==, tableContent=null), ArticleFig(id=1208478677147435410, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1208402654896697783, language=CN, label=Figure 1, caption=
The scheme of the mechanism of effect of tumor microenvironmentally modulated nanostructures. PDT: Photodynamic therapy; CDT: Chemodynamic therapy; TAMs: Tumor-associated macrophages; MDSCs: Myeloid derived suppressor cells; APCs: Antigen-presenting cells , figureFileSmall=k3e2+Lp0ClutqmlHbjucMA==, figureFileBig=3BEq5iXU3yLizPmY41JPxQ==, tableContent=null), ArticleFig(id=1208478677357150628, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1208402654896697783, language=EN, label=null, caption=null, figureFileSmall=B9G5X++0W+Qp508+XFc3Sw==, figureFileBig=DwRc5w5M0mKpXlQlrqcKng==, tableContent=null), ArticleFig(id=1208478677482979757, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1208402654896697783, language=CN, label=Figure 2, caption=
a: The changes in pH of HT1080 tumor model following treatment with nano-CaCO<sub>3</sub>. (Adapted from Ref. 15 with permission. Copyright © 2016 The Royal Society of Chemistry); b: The mechanism of effect of cationic lipid nanoparticles. (Adapted from Ref. 18 with permission. Copyright © 2019 American Chemical Society). LDHA: Lactate dehydrogenase A; MCT4: Monocarboxylate transporter 4; siLdha: siRNAs against Ldha; IFN-<i>γ</i>: Interferon <i>γ</i> , figureFileSmall=B9G5X++0W+Qp508+XFc3Sw==, figureFileBig=DwRc5w5M0mKpXlQlrqcKng==, tableContent=null), ArticleFig(id=1208478677604614587, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1208402654896697783, language=EN, label=null, caption=null, figureFileSmall=mfD7me0j5kNvU3VW6rXoHw==, figureFileBig=KW+plW7OcxNmWJPuuZGLYg==, tableContent=null), ArticleFig(id=1208478677726249419, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1208402654896697783, language=CN, label=Figure 3, caption=
a: The changes of O<sub>2</sub> concentrations in phosphate buffered saline (PBS) after treatment of oxygen-presaturated water, artificial natural killer cells (aNK), aNK(O<sub>2</sub>) and aNK(O<sub>2</sub>)+glucose. (Adapted from Ref. 20 with permission. Copyright © 2019 Wiley); b: The scheme of the mechanism of effect of HAOP. (Adapted from Ref. 22 with permission. Copyright © 2015 American Chemical Society). c(RGDfK): Tumor targeting ligand; BHQ-3: Black hole quencher-3; MB: Methylene blue; <sup>1</sup>O<sub>2</sub>: Singlet oxygen , figureFileSmall=mfD7me0j5kNvU3VW6rXoHw==, figureFileBig=KW+plW7OcxNmWJPuuZGLYg==, tableContent=null), ArticleFig(id=1208478677835301340, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1208402654896697783, language=EN, label=null, caption=null, figureFileSmall=arjmz+tmOR3RwdPxv9N7Mg==, figureFileBig=NQR3d1EEcN6rK3zmCr2VYg==, tableContent=null), ArticleFig(id=1208478677977907692, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1208402654896697783, language=CN, label=Figure 4, caption=
a: The scheme of fabrication of bMSN(CpG/Ce6)-neoantigen and mechanism of bMSN(CpG/Ce6)-neoantigen nanovaccines for cancer immunotherapy; b: The yield of <sup>1</sup>O<sub>2</sub> after treatment of bMSN, free Ce6 and bMSN(Ce6). (Adapted from Ref. 26 with permission. Copyright © 2019 American Chemical Society). bMSN: Biodegradable mesoporous silica nanoparticles; Ce6: Chlorin e6; CpG ODN: CpG oligodeoxynucleotide; PET: Positron emission tomography; SOSG: Singlet oxygen sensor green , figureFileSmall=arjmz+tmOR3RwdPxv9N7Mg==, figureFileBig=NQR3d1EEcN6rK3zmCr2VYg==, tableContent=null), ArticleFig(id=1208478678154068471, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1208402654896697783, language=EN, label=null, caption=null, figureFileSmall=1nihxvc5nEE0NK1FRoYXUQ==, figureFileBig=+mbS0Dq9ZMWV5U+KHMbGGw==, tableContent=null), ArticleFig(id=1208478678300869126, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1208402654896697783, language=CN, label=Figure 5, caption=
a: The scheme of the mechanism of effect of AIO RNAi. (Adapted from Ref. 30 with permission. Copyright © 2017 Wiley); b: The scheme of the mechanism of effect of MS@MnO<sub>2</sub>. (Adapted from Ref. 32 with permission. Copyright © 2018 Wiley). AIO: Amorphous iron oxide; EPR: Enhanced permeability and retention effect; ADS: Antioxidant defense system; GSSG: Glutathione disulfide; MRI: Nuclear magnetic resonance imaging , figureFileSmall=1nihxvc5nEE0NK1FRoYXUQ==, figureFileBig=+mbS0Dq9ZMWV5U+KHMbGGw==, tableContent=null), ArticleFig(id=1208478678443475477, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1208402654896697783, language=EN, label=null, caption=null, figureFileSmall=9yXIdjEpWhTqQzCv6VakWQ==, figureFileBig=1qJeZntygDILFMbizUi5tw==, tableContent=null), ArticleFig(id=1208478678598664746, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1208402654896697783, language=CN, label=Figure 6, caption=
a: The scheme of the mechanism of effect of DLNP; b: The concentrations of CD8<sup>+</sup> T cell in the tumors by flow cytometry analysis after treatment of different samples; c: The changes of tumor volume after treatment of different samples. (Adapted from Ref. 36 with permission. Copyright © 2019 American Chemical Society); d: The concentrations of M1 cells and M2 cells after treatment of different samples, F4/80<sup>+</sup>CD86<sup>+</sup> represent M1 macrophages and F4/80<sup>+</sup>CD206<sup>+</sup> represent M2 macrophages. (Adapted from Ref. 43 with permission. Copyright © 2020 Wiley). DLNP: Dual-locking nanoparticles; Cas13a: CRISPR-associated enzyme; PEI: Polyethyleneimine; DOX: Doxorubicin; D-LCA: Low molecular weight heparin-chrysin nanodrug (LCY) with DSPE-PEG-anisamide decoration; GLnano: Gemini-like nanodrugs , figureFileSmall=9yXIdjEpWhTqQzCv6VakWQ==, figureFileBig=1qJeZntygDILFMbizUi5tw==, tableContent=null), ArticleFig(id=1208478678707716667, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1208402654896697783, language=EN, label=null, caption=null, figureFileSmall=YuwixKvm01rcEeifcAdl2A==, figureFileBig=HbwWEUB928+hqTmm+hJjBw==, tableContent=null), ArticleFig(id=1208478678799991370, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1208402654896697783, language=CN, label=Figure 7, caption=
a: The scheme of the mechanism of effect of PLT/DOX/<i>α</i>GC NPs. (Adapted from Ref. 47 with permission. Copyright © 2020 American Chemical Society); b: The scheme of the mechanism of effect of HCP+CpG@NPs-CD80 Ab. (Adapted from Ref. 52 with permission. Copyright © 2019 Wilely). PLT/DOX/<i>α</i>GC NPs: Phenylboronic acid-modified and doxorubicin/<i>α</i>-galactosylceramide-coloaded nanoparticles; HCP+CpG@NPs-CD80 Ab: Nanoparticles loaded with HSP70‐chaperoned polypeptides and oligodeoxynucleotides containing demethylated CpG motifs and modified by antibody against CD80; LMWH: Low molecular weight heparin; TOS: Tocopherol succinate nanoparticle; IL-10: Interleukin-10; LT NP: Low molecular weight heparin-tocopherol succinate nanoparticle; PCL-Hyd-PEG: Poly (<i>ε</i>-caprolactone)-block-poly (ethylene glycol); IL-12: Interleukin-12; TNF-<i>α</i>: Tumor necrosis factor-<i>α</i>; TLR9: Toll-like receptor 9 , figureFileSmall=YuwixKvm01rcEeifcAdl2A==, figureFileBig=HbwWEUB928+hqTmm+hJjBw==, tableContent=null), ArticleFig(id=1208478678938403417, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1208402654896697783, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
| Sample | Normal cell | Tumor cell |
| pH | ~7.4 | 6.5-6.9 |
| Oxygen | 2%-9% | < 2% |
| ROS | 20 nmol·L-1 | 10 mmol·L-1 |
| Reducing substances (which mainly refer to GSH) | ~2 μmol·L-1 | ~10 μmol·L-1 |
| Immunosuppression | - | VEGF overexpression, VEGF-R activation and externalisation of phosphatidylserine |
), ArticleFig(id=1208478679039066725, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1208402654896697783, language=CN, label=Table 1, caption=
Differences between normal cells and tumor cells in pH, the concentration of oxygen, reactive oxygen species (ROS) and reducing substances and immunosuppression. GSH: Glutathione; VEGF: Vascular endothelial growth; VEGF-R: VEGF receptor
, figureFileSmall=null, figureFileBig=null, tableContent=
| Sample | Normal cell | Tumor cell |
| pH | ~7.4 | 6.5-6.9 |
| Oxygen | 2%-9% | < 2% |
| ROS | 20 nmol·L-1 | 10 mmol·L-1 |
| Reducing substances (which mainly refer to GSH) | ~2 μmol·L-1 | ~10 μmol·L-1 |
| Immunosuppression | - | VEGF overexpression, VEGF-R activation and externalisation of phosphatidylserine |
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