Article(id=1322276081311273573, tenantId=1146029695717560320, journalId=1220038251117760515, issueId=1322276007797702769, articleNumber=null, orderNo=null, doi=10.11868/j.issn.1001-4381.2024.000562, pmid=null, cstr=32421.14.j.issn.1001-4381.2024.000562, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1723392000000, receivedDateStr=2024-08-12, revisedDate=null, revisedDateStr=null, acceptedDate=1728403200000, acceptedDateStr=2024-10-09, onlineDate=1793184784486, onlineDateStr=2026-10-28, pubDate=1789833600000, pubDateStr=2026-09-20, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793184784486, onlineIssueDateStr=2026-10-28, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793184784486, creator=13701087609, updateTime=1793184784486, updator=13701087609, issue=Issue{id=1322276007797702769, tenantId=1146029695717560320, journalId=1220038251117760515, year='2026', volume='54', issue='9', pageStart='1', pageEnd='252', issueExtLink='null', onlineDate='null', pubDate='1789833600000', pubDateStr='2026-09-20', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=1, specialIssue=0, createTime=1793184766959, creator='13701087609', updateTime=1793185369041, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1322278533200728093, tenantId=1146029695717560320, journalId=1220038251117760515, issueId=1322276007797702769, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1322278533200728094, tenantId=1146029695717560320, journalId=1220038251117760515, issueId=1322276007797702769, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=244, endPage=252, ext={EN=ArticleExt(id=1322276082032693862, articleId=1322276081311273573, tenantId=1146029695717560320, journalId=1220038251117760515, language=EN, title=Synthesis of multifunctional cuttlefish-ink@CuO composite nanomaterials for photothermal-chemodynamic therapy of cancer cells, columnId=1220689384450478826, journalTitle=Journal of Materials Engineering, columnName=RESEARCH ARTICLE, runingTitle=null, highlight=null, articleAbstract=

Nanomaterials with combined photothermal-chemodynamic therapy (PTT-CDT) offer significant advantages in cancer treatment, yet designing and fabricating such multifunctional nanomaterials remains challenging. In this study, cuttlefish ink (M) is used as a core, onto which a layer of CuO is grown, successfully constructing the M@CuO composite multifunctional nanomaterial. The results show that the M@CuO exhibits a spherical shape with a nanoparticle size of 128.2 nm and demonstrates excellent photothermal conversion efficiency (ηT=47.6%) under near-infrared light irradiation. Additionally, the M@CuO shows a strong Fenton effect at room temperature (25 ℃), and the Fenton reaction rate can be further enhanced by the photothermal effect, with the reaction rate at 45 ℃ being 2.3 times that at 25 ℃ under the same conditions. In vitro cell experiments reveal that M@CuO has good biocompatibility and can effectively kill tumor cells through combined PTT-CDT. Therefore, M@CuO provides an effective strategy for developing multifunctional nanomaterials with PTT-CDT synergistic therapy.

, authors=Yan LI1, Wen ZHANG2, Wei WANG1, Peng GENG1, 3, Haichuang LAN1, Shuzhang XIAO1, 3, authorsList=Yan LI, Wen ZHANG, Wei WANG, Peng GENG, Haichuang LAN, Shuzhang XIAO, authorCompany=null, correspAuthors=Peng GENG, Shuzhang XIAO, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, 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=1322276085098730105, articleId=1322276081311273573, tenantId=1146029695717560320, journalId=1220038251117760515, language=CN, title=多功能墨鱼汁@氧化铜复合纳米材料的合成及应用于癌细胞的光热-化学动力学联合治疗, columnId=1220689384622445292, journalTitle=材料工程, columnName=研究论文, runingTitle=null, highlight=null, articleAbstract=

同时具有光热-化学动力学治疗(PTT-CDT)功能的纳米材料在癌症治疗中具有很大的优势,但这种多功能纳米材料的设计和制备仍然具有挑战性。本研究以墨鱼汁(M)为核心,在其外部生长一层CuO,成功构建了M@CuO复合多功能纳米材料。结果表明,M@CuO复合材料呈球形,纳米粒径为128.2 nm,在近红外光照射条件下具有良好的光热转换性能(ηT=47.6%)。此外,M@CuO在室温(25 ℃)时表现出良好的芬顿效应,且芬顿反应速率可通过光热效应进一步提高,相同条件下45 ℃时的芬顿反应速率是25 ℃时的2.3倍。在体外细胞实验中,M@CuO显示出良好的生物安全性,且在光热-化学动力学联合治疗效果下可以高效地杀死肿瘤细胞,为开发具有PTT-CDT联合治疗的多功能纳米材料提供了一种有效的策略。

, authors=李燕1, 张文2, 王玮1, 耿鹏1, 3, 兰海闯1, 肖述章1, 3, authorsList=李燕, 张文, 王玮, 耿鹏, 兰海闯, 肖述章, authorCompany=null, correspAuthors=耿鹏, 肖述章, authorNote=null, correspAuthorsNote=
耿鹏(1993—),男,讲师,博士,研究方向为纳米生物材料用于肿瘤诊疗,联系地址:湖北省宜昌市三峡大学材料与化工学院(443002),E-mail:
肖述章(1979—),男,教授,博士,研究方向为多功能纳米材料用于肿瘤诊疗和防伪应用,联系地址:湖北省宜昌市三峡大学材料与化工学院(443002),E-mail:
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Laboratory of Inorganic Nonmetallic Crystalline and Energy Conversion Materials,College of Materials and Chemical Engineering,China Three Gorges University,Yichang 443002,Hubei,China
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Reference(id=1322276106913305319, tenantId=1146029695717560320, journalId=1220038251117760515, articleId=1322276081311273573, doi=null, pmid=null, pmcid=null, year=2023, volume=6, issue=10, pageStart=2300049, pageEnd=null, url=null, language=null, rfNumber=[32], rfOrder=35, authorNames=Shao S X, Wu W F, Meng F X, journalName=Advanced Therapeutics, refType=null, unstructuredReference=Shao S X, Wu W F, Meng F X,et al.Copper-based nanomaterials:a rising star in cancer therapy[J].Advanced Therapeutics,2023,6(10):2300049., articleTitle=Copper-based nanomaterials:a rising star in cancer therapy, refAbstract=null), Reference(id=1322276106988802792, tenantId=1146029695717560320, journalId=1220038251117760515, articleId=1322276081311273573, doi=null, pmid=null, pmcid=null, year=2023, volume=328, issue=null, pageStart=122509, pageEnd=null, url=null, language=null, rfNumber=[33], rfOrder=36, authorNames=Jiang S L, Li C H, Muhammad Y, journalName=Applied Catalysis B:Environmental, refType=null, unstructuredReference=Jiang S L, Li C H, Muhammad Y,et al.Solvent-induced fabrication of Cu/MnO x nanosheets with abundant oxygen vacancies for efficient and long-lasting photothermal catalytic degradation of humid toluene vapor[J].Applied Catalysis B:Environmental,2023,328:122509., articleTitle=Solvent-induced fabrication of Cu/MnO x nanosheets with abundant oxygen vacancies for efficient and long-lasting photothermal catalytic degradation of humid toluene vapor, refAbstract=null), Reference(id=1322276107068494569, tenantId=1146029695717560320, journalId=1220038251117760515, articleId=1322276081311273573, doi=null, pmid=null, pmcid=null, year=2022, volume=14, issue=36, pageStart=40645, pageEnd=40658, url=null, language=null, rfNumber=[34], rfOrder=37, authorNames=Wang J, Ye J, Lv W B, journalName=ACS Applied Materials & Interfaces, refType=null, unstructuredReference=Wang J, Ye J, Lv W B,et al.Biomimetic nanoarchitectonics of hollow mesoporous copper oxide-based nanozymes with cascade catalytic reaction for near infrared-Ⅱ reinforced photothermal-catalytic therapy[J].ACS Applied Materials & Interfaces,2022,14(36):40645-40658., articleTitle=Biomimetic nanoarchitectonics of hollow mesoporous copper oxide-based nanozymes with cascade catalytic reaction for near infrared-Ⅱ reinforced photothermal-catalytic therapy, refAbstract=null)], funds=[Fund(id=1322276102291182272, tenantId=1146029695717560320, journalId=1220038251117760515, articleId=1322276081311273573, awardId=22171163, language=CN, fundingSource=国家自然科学基金项目(22171163), fundOrder=null, country=null), Fund(id=1322276102358291137, tenantId=1146029695717560320, journalId=1220038251117760515, articleId=1322276081311273573, awardId=2024AFB059, language=CN, fundingSource=湖北省自然科学基金项目(2024AFB059), fundOrder=null, country=null), Fund(id=1322276102421205698, tenantId=1146029695717560320, journalId=1220038251117760515, articleId=1322276081311273573, awardId=A23-2-025, language=CN, fundingSource=宜昌市自然科学研究项目(A23-2-025), 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remark=2.三峡大学 生物与制药学院,湖北 宜昌 443002)]), AuthorCompany(id=1322276085975339648, tenantId=1146029695717560320, journalId=1220038251117760515, articleId=1322276081311273573, xref=3., ext=[AuthorCompanyExt(id=1322276085987922561, tenantId=1146029695717560320, journalId=1220038251117760515, articleId=1322276081311273573, companyId=1322276085975339648, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=3.Hubei Three Gorges Laboratory,Yichang 443007,Hubei,China), AuthorCompanyExt(id=1322276085996311170, tenantId=1146029695717560320, journalId=1220038251117760515, articleId=1322276081311273573, companyId=1322276085975339648, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=3.湖北三峡实验室,湖北 宜昌 443007)])], figs=[ArticleFig(id=1322276097975243440, tenantId=1146029695717560320, journalId=1220038251117760515, articleId=1322276081311273573, language=EN, label=Fig.1, caption=Synthesized route of M@CuO and its application in the combined PTT-CDT of tumor cells, figureFileSmall=mSxYvHAv73mcvIdiqZafeA==, figureFileBig=acnn89p58l/DYrMpQmwcJA==, tableContent=null), ArticleFig(id=1322276098839270065, tenantId=1146029695717560320, journalId=1220038251117760515, articleId=1322276081311273573, language=CN, label=图1, caption=M@CuO的合成路线及其用于肿瘤细胞光热-化学动力学联合治疗, figureFileSmall=mSxYvHAv73mcvIdiqZafeA==, figureFileBig=acnn89p58l/DYrMpQmwcJA==, tableContent=null), ArticleFig(id=1322276099334197938, tenantId=1146029695717560320, journalId=1220038251117760515, articleId=1322276081311273573, language=EN, label=Fig.2, caption=Basic characterization of the samples

(a),(b)SEM image and particle size distribution of M;(c),(d)SEM image and particle size distribution of M@CuO;(e),(f)hydrodynamic dimensions and Zeta potentiogram for M and M@CuO

, figureFileSmall=WtecCZ9EPO2+VIJ/UCFtyQ==, figureFileBig=NT71zVnCWm7HM3KcJ7Myrw==, tableContent=null), ArticleFig(id=1322276099623604915, tenantId=1146029695717560320, journalId=1220038251117760515, articleId=1322276081311273573, language=CN, label=图2, caption=样品的基本表征

(a),(b)M的SEM图和粒径分布图;(c),(d)M@CuO的SEM图和粒径分布图;(e),(f)M和M@CuO的流体动力学尺寸和Zeta电位图

, figureFileSmall=WtecCZ9EPO2+VIJ/UCFtyQ==, figureFileBig=NT71zVnCWm7HM3KcJ7Myrw==, tableContent=null), ArticleFig(id=1322276101292937908, tenantId=1146029695717560320, journalId=1220038251117760515, articleId=1322276081311273573, language=EN, label=Fig.3, caption=XRD spectra(a),XPS spectra(b),(c),and UV-Vis-NIR absorption spectra(d) of M@CuO, figureFileSmall=Xvlh8tneNickwKtUOFXtcQ==, figureFileBig=wMzZ/LR/MekRX3VVWnsN/Q==, tableContent=null), ArticleFig(id=1322276101397795509, tenantId=1146029695717560320, journalId=1220038251117760515, articleId=1322276081311273573, language=CN, label=图3, caption=M@CuO的XRD图(a)、X射线光电子能谱图(b),(c)和紫外-可见-近红外吸收图(d), figureFileSmall=Xvlh8tneNickwKtUOFXtcQ==, figureFileBig=wMzZ/LR/MekRX3VVWnsN/Q==, tableContent=null), ArticleFig(id=1322276101502653110, tenantId=1146029695717560320, journalId=1220038251117760515, articleId=1322276081311273573, language=EN, label=Fig.4, caption=The photothermal conversion performance of the sample

(a)temperature change diagram of M@CuO dispersion with different concentrations under 808 nm laser irradiation;

(b)photothermal cycle stability diagram of M@CuO dispersion;(c)temperature change curves of M@CuO dispersion

under laser on/off state; (d)linear time data of M@CuO fit a straight line to lnθ

, figureFileSmall=CX3VHtySXrQy57dvt3F2zw==, figureFileBig=9xT6e2bIeBXq8L08Y1wqfQ==, tableContent=null), ArticleFig(id=1322276101578150583, tenantId=1146029695717560320, journalId=1220038251117760515, articleId=1322276081311273573, language=CN, label=图4, caption=样品的光热转换性能

(a)不同浓度M@CuO分散液在808 nm激光照射下的温度变化图;(b)M@CuO分散液的光热循环稳定图;(c)激光开/关状态下M@CuO分散液温度变化曲线;(d)M@CuO线性时间的数据对lnθ的直线拟合

, figureFileSmall=CX3VHtySXrQy57dvt3F2zw==, figureFileBig=9xT6e2bIeBXq8L08Y1wqfQ==, tableContent=null), ArticleFig(id=1322276101653648056, tenantId=1146029695717560320, journalId=1220038251117760515, articleId=1322276081311273573, language=EN, label=Fig.5, caption=Fenton-like catalytic performance of the samples

(a)schematic illustration of photothermally-enhanced Fenton reaction;(b),(c)time-dependent absorption spectra of MB mediated by M@CuO and H2O2 at 25 ℃ or 45 ℃;(d)degradation rate of MB under different conditions

, figureFileSmall=1NQziz4W2tj7foI2uqpYAA==, figureFileBig=DMPWNmMgpnaJFM/WhacFOQ==, tableContent=null), ArticleFig(id=1322276101754311353, tenantId=1146029695717560320, journalId=1220038251117760515, articleId=1322276081311273573, language=CN, label=图5, caption=样品的类Fenton催化性能

(a)光热提升化学动力学治疗示意图;(b),(c)在25 ℃或45 ℃条件下,M@CuO和H2O2介导的MB随时间依赖性吸收光谱;(d)不同条件下MB的降解速率

, figureFileSmall=1NQziz4W2tj7foI2uqpYAA==, figureFileBig=DMPWNmMgpnaJFM/WhacFOQ==, tableContent=null), ArticleFig(id=1322276101825614522, tenantId=1146029695717560320, journalId=1220038251117760515, articleId=1322276081311273573, language=EN, label=Fig.6, caption=Cytotoxicity of HUVEC(a)、CT26(b),and 4T1(c) cell treated with the M@CuO for 24 h, figureFileSmall=O+G4U74fq74NQVJNDvv2yg==, figureFileBig=1dITj7wNgLsxwD6/Chmt+Q==, tableContent=null), ArticleFig(id=1322276101905306299, tenantId=1146029695717560320, journalId=1220038251117760515, articleId=1322276081311273573, language=CN, label=图6, caption=HUVEC(a)、CT26(b)和4T1(c)细胞与不同浓度的M@CuO共培养24 h后的细胞存活率, figureFileSmall=O+G4U74fq74NQVJNDvv2yg==, figureFileBig=1dITj7wNgLsxwD6/Chmt+Q==, tableContent=null), ArticleFig(id=1322276101972415164, tenantId=1146029695717560320, journalId=1220038251117760515, articleId=1322276081311273573, language=EN, label=Fig.7, caption=The therapeutic effects of PTT and CDT for M@CuO

(a)relative viability of PTT for different time;(b)relative viability under CDT at different concentrations of M@CuO

, figureFileSmall=PPaIzvMVTpKiQXdCQmv2Bg==, figureFileBig=n6OeDlr1W8dQwZfYT78tAA==, tableContent=null), ArticleFig(id=1322276102047912637, tenantId=1146029695717560320, journalId=1220038251117760515, articleId=1322276081311273573, language=CN, label=图7, caption=M@CuO的PTT和CDT疗效

(a)PTT在不同光照时间下的细胞存活率;(b)CDT在不同M@CuO浓度下的细胞存活率

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多功能墨鱼汁@氧化铜复合纳米材料的合成及应用于癌细胞的光热-化学动力学联合治疗
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李燕 1 , 张文 2 , 王玮 1 , 耿鹏 1, 3 , 兰海闯 1 , 肖述章 1, 3
材料工程 | 研究论文 2026,54(9): 244-252
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材料工程 |研究论文 2026 , 54 (9) : 244 -252
多功能墨鱼汁@氧化铜复合纳米材料的合成及应用于癌细胞的光热-化学动力学联合治疗
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李燕1, 张文2, 王玮1, 耿鹏1, 3 , 兰海闯1, 肖述章1, 3
作者信息
  • 1.三峡大学 材料与化工学院 无机非金属晶态与能源转换材料重点实验室,湖北 宜昌 443002
  • 2.三峡大学 生物与制药学院,湖北 宜昌 443002
  • 3.湖北三峡实验室,湖北 宜昌 443007
通讯作者:
耿鹏(1993—),男,讲师,博士,研究方向为纳米生物材料用于肿瘤诊疗,联系地址:湖北省宜昌市三峡大学材料与化工学院(443002),E-mail:
肖述章(1979—),男,教授,博士,研究方向为多功能纳米材料用于肿瘤诊疗和防伪应用,联系地址:湖北省宜昌市三峡大学材料与化工学院(443002),E-mail:
Synthesis of multifunctional cuttlefish-ink@CuO composite nanomaterials for photothermal-chemodynamic therapy of cancer cells
Yan LI1, Wen ZHANG2, Wei WANG1, Peng GENG1, 3 , Haichuang LAN1, Shuzhang XIAO1, 3
Affiliations
  • 1.Key Laboratory of Inorganic Nonmetallic Crystalline and Energy Conversion Materials,College of Materials and Chemical Engineering,China Three Gorges University,Yichang 443002,Hubei,China
  • 2.College of Biological and Pharmaceutical Sciences,China Three Gorges University,Yichang 443002,Hubei,China
  • 3.Hubei Three Gorges Laboratory,Yichang 443007,Hubei,China
出版时间: 2026-09-20 doi: 10.11868/j.issn.1001-4381.2024.000562
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同时具有光热-化学动力学治疗(PTT-CDT)功能的纳米材料在癌症治疗中具有很大的优势,但这种多功能纳米材料的设计和制备仍然具有挑战性。本研究以墨鱼汁(M)为核心,在其外部生长一层CuO,成功构建了M@CuO复合多功能纳米材料。结果表明,M@CuO复合材料呈球形,纳米粒径为128.2 nm,在近红外光照射条件下具有良好的光热转换性能(ηT=47.6%)。此外,M@CuO在室温(25 ℃)时表现出良好的芬顿效应,且芬顿反应速率可通过光热效应进一步提高,相同条件下45 ℃时的芬顿反应速率是25 ℃时的2.3倍。在体外细胞实验中,M@CuO显示出良好的生物安全性,且在光热-化学动力学联合治疗效果下可以高效地杀死肿瘤细胞,为开发具有PTT-CDT联合治疗的多功能纳米材料提供了一种有效的策略。

墨鱼汁  /  氧化铜  /  光热治疗  /  化学动力学治疗  /  联合治疗

Nanomaterials with combined photothermal-chemodynamic therapy (PTT-CDT) offer significant advantages in cancer treatment, yet designing and fabricating such multifunctional nanomaterials remains challenging. In this study, cuttlefish ink (M) is used as a core, onto which a layer of CuO is grown, successfully constructing the M@CuO composite multifunctional nanomaterial. The results show that the M@CuO exhibits a spherical shape with a nanoparticle size of 128.2 nm and demonstrates excellent photothermal conversion efficiency (ηT=47.6%) under near-infrared light irradiation. Additionally, the M@CuO shows a strong Fenton effect at room temperature (25 ℃), and the Fenton reaction rate can be further enhanced by the photothermal effect, with the reaction rate at 45 ℃ being 2.3 times that at 25 ℃ under the same conditions. In vitro cell experiments reveal that M@CuO has good biocompatibility and can effectively kill tumor cells through combined PTT-CDT. Therefore, M@CuO provides an effective strategy for developing multifunctional nanomaterials with PTT-CDT synergistic therapy.

cuttlefish ink  /  copper oxide  /  photothermal therapy  /  chemodynamic therapy  /  combined therapy
李燕, 张文, 王玮, 耿鹏, 兰海闯, 肖述章. 多功能墨鱼汁@氧化铜复合纳米材料的合成及应用于癌细胞的光热-化学动力学联合治疗. 材料工程, 2026 , 54 (9) : 244 -252 . DOI: 10.11868/j.issn.1001-4381.2024.000562
Yan LI, Wen ZHANG, Wei WANG, Peng GENG, Haichuang LAN, Shuzhang XIAO. Synthesis of multifunctional cuttlefish-ink@CuO composite nanomaterials for photothermal-chemodynamic therapy of cancer cells[J]. Journal of Materials Engineering, 2026 , 54 (9) : 244 -252 . DOI: 10.11868/j.issn.1001-4381.2024.000562
癌症因其高发病率和死亡率严重威胁人们的生命安全和健康,为了高效治疗癌症,近年来开发了多种新型治疗策略[1-3]。这些治疗方法主要包括:光动力治疗(PDT)[4-5]、光热治疗(PTT)[6-7]、声动力治疗(SDT)[8-9]和化学动力治疗(CDT)[10-11]等。然而,每种治疗方法虽然有其独特的优势,但也会存在一些不足。例如,PTT主要是借助近红外(NIR)光来产生热促使癌细胞死亡[12-13],但NIR光的生物组织穿透力较弱,只能治疗浅表的癌细胞,且当激发光停止照射时,PTT效果也将立即停止,无法长期抑制肿瘤,肿瘤易复发[14-15]。此外,肿瘤的复杂性和多样性进一步限制了基于纳米药物的单一治疗效果,导致目前肿瘤临床研究的趋势是从单一治疗转向综合协同治疗,以提高整体疗效[16-18]。
为了弥补单一光热治疗效果的不足,本课题组近期开发了一种墨鱼汁-原卟啉纳米复合物(CIPs),该CIPs对肿瘤细胞能进行有效的PTT-SDT联合治疗[19]。SDT治疗模式中超声的组织穿透深度较大(>10 cm),可以有效地治疗深部肿瘤;但同样存在超声停止激发后治疗效果也立即停止的问题,肿瘤易复发[20-21]。CDT是利用纳米材料本身与肿瘤微环境中的H2O2反应生成剧毒的羟基自由基(·OH)来杀死肿瘤细胞,该治疗方法不仅可以治疗深部肿瘤细胞,而且可以长时间持续地产生化学动力学疗效;但CDT经Fenton反应产生·OH的速率较低,导致CDT的疗效不理想[22-23]。而联合使用PTT与CDT时,不仅可以弥补各自的不足,还可通过PTT提升温度和Fenton反应生成·OH速率,从而增强CDT的治疗效果[24-25]。PTT-CDT联合治疗的关键,是开发具有显著光热转换性能和化学动力学效果的多功能纳米材料[26-28]。
墨鱼汁主要是由C、N、O等元素组成的无定型碳,且表面含有丰富的—OH、—C═O—、—C═C—等基团。墨鱼汁由于其天然的生物相容性和生物降解性,被认为是一种优秀的光热试剂[29-30]。此外,铜基纳米材料已经被证实为有效的Fenton试剂,铜催化的Fenton反应在弱酸性和中性条件下的催化效率更高,是铁基纳米材料介导的Fenton反应速率的160倍[31-32]。因此,本研究构造了一种多功能墨鱼汁@氧化铜复合纳米材料(M@CuO)用于癌细胞治疗。研究结果显示,M@CuO不仅具有良好的PTT和CDT效果,且CDT性能可进一步通过PTT效果显著提升,实现高效的PTT-CDT联合治疗效果(图1)。
二水合氯化铜(CuCl2·2H2O),分析纯,上海麦克林生化科技股份有限公司;氢氧化钠(NaOH),分析纯,国药集团化学试剂有限公司;聚乙烯吡咯烷酮(PVP-K30),分析纯,上海麦克林生化科技股份有限公司;亚甲基蓝(MB),分析纯,上海麦克林生化科技股份有限公司;乙醇(CH3CH2OH),分析纯,上海阿拉丁生化科技股份有限公司;4',6-二脒基-2-苯基吲哚(DAPI),分析纯,上海麦克林生化科技股份有限公司;磷酸缓冲盐溶液(PBS),分析纯,上海麦克林生化科技股份有限公司;2′,7′-二氯荧光素二乙酸酯(DCFH-DA)),分析纯,上海麦克林生化科技股份有限公司;四甲基偶氮唑蓝(MTT),分析纯,上海麦克林生化科技股份有限公司。
墨鱼汁(M)来源于新鲜墨鱼的墨囊,经过清洗、离心获得。随后取5 mg的M加入NaOH溶液(5 mL,pH=12)中搅拌12 h,随后将离心后的纳米颗粒加入CuSO4溶液(5 mL,0.1 mol·L-1)中,磁力搅拌5 min,抽滤,干燥,最后在350 ℃下煅烧5 h,得到的黑色颗粒即墨鱼汁@氧化铜复合纳米材料。
光热转换性能测试:首先,配制不同浓度(0、0.05、0.1、0.2、0.4 mg·mL-1)的M@CuO水分散液,再用808-A型半导体激光器(808 nm,1.0 W·cm-2)对准不同浓度的M@CuO分散液并用热成像相机监测分散液的温度变化。
光稳定性测试:用808 nm激光器开-关4次(20 min/次)照射浓度为0.1 mg·mL-1的M@CuO分散液并用热成像相机监测4个周期内分散液的温度变化情况。
为了进一步评估光热转换效率,用808 nm激光照射M@CuO(100 μL)分散液。激光照射分散液600 s使温度达到平衡(稳态最高温度Tmax=55.8 ℃),然后关闭激光,让温度降至室温(Tsur=27.6 ℃)。根据Roper的报告,通过改进的方法计算光热转换效率(ηT),见式(1)。
ηT=hATmax-Tsur-QdisI1-10-A808×100%
式中:h、A和I是传热系数、容器的表面积和激光功率;Qdis为溶剂吸收的热量,W;吸光度(A808)计算为0.33。hA可以从下面等式计算:
τs=mH2OCH2OhA
式中:τs是系统时间常数(169.1 s);mH2O和CH2O表示去离子水的质量(0.1 g)和热容(4.2 J·g-1)。在类似条件下使用水可以独立测试Qdis为0.0019。
引入无量纲驱动力参数θ:
θ=T-TsurTmax-Tsur
对lnθ与时间τ进行线性拟合,得到时间常数τs。
配制90 mL浓度为0.005 mg·mL-1的亚甲基蓝(MB)水溶液和0.1 mg·mL-1的M@CuO水分散液,将混合溶液在黑暗条件下搅拌30 min,以达到吸附-脱附平衡。随后,将混合溶液(M@CuO+MB)均匀分成三等份,分为3个测试组:(1)M@CuO+MB(25 ℃);(2)M@CuO+MB+H2O2(25 ℃);(3)M@CuO+MB+H2O2(45 ℃)。(2)和(3)中分批次且加入等量的H2O2,每次间隔5 min通过UV2600型紫外-可见分光光度计测试并记录其在650 nm的紫外-可见吸收光谱。
人脐静脉内皮细胞(HUVEC)、小鼠结肠癌细胞(CT26)和小鼠乳腺癌细胞(4T1)等细胞系在标准条件下以1×104/孔接种于96孔板中孵育12 h,然后用含有一系列不同浓度M@CuO纳米颗粒(NPs)的新鲜培养基更换旧培养基,继续孵育24 h或48 h后用磷酸缓冲盐溶液(PBS)洗涤细胞并使用标准MTT法评估细胞存活率。
细胞光热治疗(PTT):首先将培养细胞的96孔板与含有0.2 mg·mL-1的M@CuO的新鲜培养基共孵育4 h。然后,对细胞进行不同时间的NIR光(808 nm)照射以进行肿瘤细胞光热治疗。最后,通过使用标准的四甲基偶氮唑蓝(MTT)法评估光热治疗后细胞的存活率,使用Calcine-AM/PI染色法对治疗后的细胞进行共染色,并拍摄细胞荧光图像。
细胞化学动力学治疗(CDT):将培养好细胞的两块96孔板弃去旧培养基并用PBS清洗一遍。一块板用新鲜培养基中含有不同浓度的M@CuO(0~0.2 mg·mL-1,150 μL)代替。另一块板用新鲜培养基中含有不同浓度的M@CuO(0~0.2 mg·mL-1, 150 μL)和H2O2(100 μmol·L-1)代替。两块96孔板一起放入细胞培养箱中共孵育12 h后,丢弃旧培养基,通过MTT法测试细胞存活率。此外,使用Calcine-AM/PI染色法对细胞进行共染色,并拍摄荧光图像。
细胞体外联合治疗:将4T1细胞接种于多个96孔板(1×104个细胞/孔),培养12 h。随后,将培养的细胞随机分为7组:(1)Control组;(2)M@CuO组;(3)NIR照射组;(4)H2O2组;(5)M@CuO+NIR;(6)M@CuO+H2O2;(7)M@CuO+H2O2+NIR。各组经过不同处理后,用PBS洗涤细胞,并通过标准MTT法评估细胞存活率。此外进行细胞Calcein-AM/PI共染色,然后用荧光显微镜拍摄荧光图像。
首先对复合材料M@CuO的形貌和尺寸进行了表征。JSM-7500F型扫描电子显微镜(SEM)显示,从新鲜墨鱼的墨囊中提取的M呈颗粒大小均匀的球形,纳米直径约(105.6±2.3) nm (图2(a),(b))。形成复合材料M@CuO后依然呈球形结构,粒径在(128.2±1.9) nm,略大于纯墨鱼汁的纳米直径,这可能是由于M表面CuO的形成增大了纳米直径所致(图2(c),(d))。随后,通过NANOTRAC WAVEⅡ型纳米粒度及Zeta电位分析仪进一步测量了M和M@CuO纳米材料的流体动力学尺寸和Zeta电位。结果显示,M的流体动力学直径为259.7 nm,表面电位为-17.6 mV;而M@CuO的流体动力学直径为289.3 nm,表面电位为-9.7 mV,同样是由于M表面CuO的形成增大了纳米直径和减小了表面电位所致(图2(e),(f))。综上所述,复合材料M@CuO依然呈球形,但纳米直径相较于M会略有增加。
随后采用Bruker D4型射线衍射仪(XRD)和AXIS Supra型X射线光电子能谱仪(XPS)等进一步研究了M@CuO的物质组成与结构。XRD结果显示,M@CuO在35.4°、38.5°、48.7°、66.4°、68.1°处展现了强烈的特征衍射峰,与CuO的标准XRD卡片峰(PDF 44-0706)相一致[33],表明成功在墨鱼汁表面生长了一层CuO(图3(a))。XPS总谱显示了来自C、Cu和O元素的强信号,其中C来源于墨鱼汁,Cu和O来源于表面的CuO(图3(b))。Cu 2p谱图分别在955.4 eV和935.3 eV附近显示出2个峰值,它们分别对应于Cu2+态的Cu 2p1/2和Cu 2p3/2。此外,在963.2、944.5 eV和940.5 eV附近的3个峰为+2价Cu盐的特征峰(图3(c))[34]。因此,M@CuO样品中的Cu元素为+2价,与XRD中对应的化学式结果相一致。最后,通过紫外-可见-近红外光谱测量了M和M@CuO的光学性质。结果显示,M@CuO在400~1000 nm处表现出较强的光吸收。值得注意的是,与纯M相比,M@CuO在近红外部分(800~1000 nm)的光吸收与M相同,表明形成M@CuO后并未影响M在近红外的光吸收效果(图3(d))。因此,本团队后续采用808 nm激光研究其光热性能。
首先,研究了不同浓度M@CuO分散液(0~0.4 mg·mL-1)在808 nm激光照射(1.0 W·cm-2)时的光热转换性能。图4显示了样品的光热转换性能。从图4(a)中可以看出,M@CuO分散液在光照下的升温效果呈浓度依赖性,纯水在10 min内仅升温3.9 ℃,而M@CuO(0.4 mg·mL-1)在10 min内升温62.5 ℃, 表明M@CuO分散液在808 nm激光照射下具有良好的光热转换性能。此外,将浓度为0.1 mg·mL-1的M@CuO分散液置于不同激光功率下(0.2~1 W·cm-2),监测其温度变化图。结果发现,随着功率的增加,M@CuO分散液的升温效果愈发明显,ΔT从0.2 W·cm-2时的3.4 ℃增加到1 W·cm-2时的38.3 ℃,表明M@CuO分散液不仅具有浓度依赖性的光热性能还具有激光功率依赖性的光热性能。而且,M@CuO分散液的平衡温度在经过4次808 nm激光开/关循环后没有明显变化,显示出优异的光热循环稳定性(图4(b))。最后,通过对M@CuO分散液升/降温过程的数据点进行线性拟合,研究了M@CuO的光热转换效率(图4(c),(d))。M@CuO分散液(0.1 mg·mL-1)经受808 nm激光(1 W·cm-2)600 s达到平衡温度(Tmax=55.8 ℃),然后关闭激光器,温度降至初始温度(Tsur=27.6 ℃)。经式(1)计算,M@CuO的光热转换效率为47.6%。综上所述,M@CuO具有优异的光热转换性能,可作为潜在的光热材料用于肿瘤治疗。
Cu元素可以通过Fenton反应催化H2O2生成高活性的·OH。在升高温度时,活性H2O2分子比例会增加,提高Fenton反应速率,从而产生更多的·OH(图5(a))。本工作采用MB比色法研究了M@CuO的光热增强Fenton反应速率。首先将含有M@CuO(100 μg·mL-1)和MB(0.005 mg·mL-1)的混合溶液在黑暗条件下持续搅拌30 min,达到吸附-脱附平衡。随后,将H2O2加入吸附-脱附平衡后的混合物(M@CuO+MB)中,研究其在不同条件下的Fenton反应速率。在不加H2O2的条件下,混合物(吸附-脱附平衡)中MB的特征吸收峰并没有发生任何变化,表明纯M@CuO没有产生·OH的性能。但是,当在室温(25 ℃)条件下加入H2O2后,混合物中MB的特征吸收峰吸光度在30 min内从1.64缓慢下降到1.17(图5(b)),表明M@CuO在室温下能有效催化H2O2生成·OH。作为比较,在45 ℃水浴条件下(模拟光热升温效果)进行相同浓度/反应时间的Fenton反应。结果显示,混合物中MB的特征吸收峰吸光度在30 min内从1.64迅速下降到0.55(图5(c)),表明M@CuO在45 ℃下能持续、高效地催化H2O2生成·OH。经计算,在相同条件下,混合物M@CuO+MB+H2O2在45 ℃下降解MB的效率为66.5%,是25 ℃时(28.7%)的2.3倍(图5(d))。因此,M@CuO能有效催化H2O2生成·OH,且能通过光热效应进一步增强。
良好的生物相容性是生物纳米材料应用的前提。为此,本研究将人脐静脉内皮细胞(HUVEC)、小鼠结肠癌细胞(CT26)和小鼠乳腺癌细胞(4T1)分别与含有不同浓度的M@CuO(0~400 μg·mL-1)共孵育,以评估其细胞相容性(图6)。结果显示,经过共孵育24 h后,与M@CuO培养的非癌细胞HUVEC和癌细胞CT26、4T1均表现为高水平的细胞存活率(>85%),表明M@CuO对体外细胞具有良好的生物安全性。
随后将4T1细胞与M@CuO(200 μg·mL-1)共孵育12 h,然后用细胞活力检测试剂盒(MTT)测试其在光照条件下的PTT效果。在808 nm激光照射条件下(1.0 W·cm-2),3 min后细胞仍显示出较高的存活率(87.4%),但随光照时间的增加,细胞存活率逐渐降低为41.3%(6 min)和16.1%(9 min),表明M@CuO在NIR光照射条件下具有良好的PTT效果,且可以通过调节光照时间达到目标效果(图7(a))。此外,还通过MTT检测法研究了不同浓度的M@CuO在体外化学动力学治疗的抗癌效果。显然,当4T1细胞与M@CuO共孵育12 h后,在给定浓度(0~200 μg·mL-1)范围内,细胞活性均超过85%。相反,当细胞与M@CuO+H2O2共孵育12 h后,细胞活性从0 μg·mL-1时的100%下降到200 μg·mL-1时的51.7%,这表明M@CuO与H2O2结合具有良好的CDT效果,且CDT效果呈剂量依赖性(图7(b))。
为了评估体外光热-化学动力学联合治疗效果,使用含有M@CuO(200 μg·mL-1)的DMEM培养基孵育4T1细胞12 h,其中部分组采用808 nm激光照射(1 W·cm-2,6 min)且/或加入H2O2(100 μmol/L)。这些细胞共分为7组,具体见1.7节。这些组都通过MTT法检测细胞存活率并用荧光显微镜观察细胞荧光染色照片(图8)。在组(1)~(4)中,细胞存活率均超过85%,表明单独使用M@CuO、NIR或H2O2对癌细胞4T1没有杀伤效果。但是,组(5)细胞的细胞存活率为41.3%,表明M@CuO在NIR光照射下具有良好的PTT效果。此外,组(6)细胞的细胞存活率下降至52.8%,确认了良好的CDT效果。更重要的是,组(7)的细胞存活率最低,仅为19.2%,这归因于良好的协同PTT-CDT治疗效果(图8(a))。同时荧光照片显示,组(1)~(4)的细胞几乎全为绿色荧光(活细胞)。相较于组(1)~(4),组(5)~(7)中的细胞绿色荧光区域减少,而红色荧光(死细胞)区域迅速增加,这表明癌细胞存活率下降。特别是,M@CuO+H2O2+NIR组(7)显示出多数死亡细胞的红色荧光(图8(b))。此外,对另一种癌细胞CT26也采用标准MTT法研究了其在不同治疗条件下的细胞存活率。研究发现,单独使用M@CuO、NIR或H2O2对癌细胞CT26没有杀伤效果。但组(5)和组(6)的CT26细胞存活率分别为44.7%和49.1%,表明M@CuO具有良好的PTT效果和CDT效果。且组(7)的细胞存活率仅为21.4%,表明PTT-CDT联合治疗具有最佳的治疗效果。综上所述,M@CuO与NIR光和H2O2结合,具有优异的光热-化学动力学联合治疗功效,可以高效地杀死肿瘤细胞。
(1)成功制备了多功能M@CuO复合纳米材料用于肿瘤光热-化学动力学联合治疗(PTT-CDT)。M@CuO呈球形结构,粒径在128.2 nm,略大于纯墨鱼汁的纳米直径(105.6 nm)。
(2)M@CuO在808 nm处表现出良好的近红外光吸收和良好的光热转换效率(ηT=47.6%)。此外,M@CuO表现出芬顿反应特征(25 ℃),且反应速率可进一步通过光热效应(45 ℃)显著提高(2.3倍)。
(3)将M@CuO分散液与细胞共孵育显示出良好的生物安全性,且在光热-化学动力学联合治疗效果下可以高效地杀死肿瘤细胞。
  • 国家自然科学基金项目(22171163)
  • 湖北省自然科学基金项目(2024AFB059)
  • 宜昌市自然科学研究项目(A23-2-025)
  • 111项目(D20015)
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doi: 10.11868/j.issn.1001-4381.2024.000562
  • 接收时间:2024-08-12
  • 首发时间:2026-10-28
  • 出版时间:2026-09-20
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  • 收稿日期:2024-08-12
  • 录用日期:2024-10-09
基金
国家自然科学基金项目(22171163)
湖北省自然科学基金项目(2024AFB059)
宜昌市自然科学研究项目(A23-2-025)
111项目(D20015)
作者信息
    1.三峡大学 材料与化工学院 无机非金属晶态与能源转换材料重点实验室,湖北 宜昌 443002
    2.三峡大学 生物与制药学院,湖北 宜昌 443002
    3.湖北三峡实验室,湖北 宜昌 443007

通讯作者:

耿鹏(1993—),男,讲师,博士,研究方向为纳米生物材料用于肿瘤诊疗,联系地址:湖北省宜昌市三峡大学材料与化工学院(443002),E-mail:
肖述章(1979—),男,教授,博士,研究方向为多功能纳米材料用于肿瘤诊疗和防伪应用,联系地址:湖北省宜昌市三峡大学材料与化工学院(443002),E-mail:
参考文献
分享链接
https://castjournals.cast.org.cn/joweb/clgc/CN/10.11868/j.issn.1001-4381.2024.000562
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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
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