{"title":"构建基于自噬抑制和光动力疗法的多功能上转换纳米平台,结合化疗进行抗肿瘤治疗","authors":"Fang Ning, Dengshuai Wei, Hongli Yu, Tingting Song, Zhipeng Li, Hongmei Ma, Yong Sun","doi":"10.1021/acs.molpharmaceut.4c00203","DOIUrl":null,"url":null,"abstract":"<p><p>Inhibition of autophagy increases the sensitivity of tumor cells to radiotherapy and chemotherapy and improves the therapeutic effect on tumors. Recently, photodynamic therapy (PDT) combined with chemotherapy has been proven to further improve the efficiency of cancer treatment. As such, combining autophagy inhibition with PDT and chemotherapy may represent a potentially effective new strategy for cancer treatment. However, currently widely studied autophagy inhibitors inevitably produce various toxic side effects due to their inherent pharmacological activity. To overcome this constraint, in this study, we designed an ideal multifunctional upconversion nanoplatform, UCNP-Ce6-EPI@mPPA + NIR (MUCEN). Control, UCNP-EPI@mPPA (MUE), UCNP-EPI@mPPA + NIR (MUEN), Ce6-EPI@mPPA (MCE), Ce6-EPI@mPPA + NIR (MCEN), and UCNP-Ce6-EPI@mPPA (MUCE) groups were set up separately as controls. Based on a combination of autophagy inhibition and PDT, the average particle size of MUCEN was 197 nm, which can simultaneously achieve the double encapsulation of chlorine e6 (Ce6) and epirubicin (EPI). In vitro tests revealed that MUCE was efficiently endocytosed by 4T1 cells under near-infrared light irradiation. Further, in vivo tests revealed that MUCE dramatically inhibited tumor growth. Immunohistochemistry results indicated that MUCE efficiently increased the expression of autophagy inhibitors p62 and LC3 in tumor tissues. The synergistic effect of autophagy inhibition and PDT with MUCE exhibited superior tumor suppression, providing an innovative approach to cancer treatment.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":4.5000,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Construction of a Multifunctional Upconversion Nanoplatform Based on Autophagy Inhibition and Photodynamic Therapy Combined with Chemotherapy for Antitumor Therapy.\",\"authors\":\"Fang Ning, Dengshuai Wei, Hongli Yu, Tingting Song, Zhipeng Li, Hongmei Ma, Yong Sun\",\"doi\":\"10.1021/acs.molpharmaceut.4c00203\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Inhibition of autophagy increases the sensitivity of tumor cells to radiotherapy and chemotherapy and improves the therapeutic effect on tumors. Recently, photodynamic therapy (PDT) combined with chemotherapy has been proven to further improve the efficiency of cancer treatment. As such, combining autophagy inhibition with PDT and chemotherapy may represent a potentially effective new strategy for cancer treatment. However, currently widely studied autophagy inhibitors inevitably produce various toxic side effects due to their inherent pharmacological activity. To overcome this constraint, in this study, we designed an ideal multifunctional upconversion nanoplatform, UCNP-Ce6-EPI@mPPA + NIR (MUCEN). Control, UCNP-EPI@mPPA (MUE), UCNP-EPI@mPPA + NIR (MUEN), Ce6-EPI@mPPA (MCE), Ce6-EPI@mPPA + NIR (MCEN), and UCNP-Ce6-EPI@mPPA (MUCE) groups were set up separately as controls. Based on a combination of autophagy inhibition and PDT, the average particle size of MUCEN was 197 nm, which can simultaneously achieve the double encapsulation of chlorine e6 (Ce6) and epirubicin (EPI). In vitro tests revealed that MUCE was efficiently endocytosed by 4T1 cells under near-infrared light irradiation. Further, in vivo tests revealed that MUCE dramatically inhibited tumor growth. Immunohistochemistry results indicated that MUCE efficiently increased the expression of autophagy inhibitors p62 and LC3 in tumor tissues. The synergistic effect of autophagy inhibition and PDT with MUCE exhibited superior tumor suppression, providing an innovative approach to cancer treatment.</p>\",\"PeriodicalId\":52,\"journal\":{\"name\":\"Molecular Pharmaceutics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2024-09-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Pharmaceutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1021/acs.molpharmaceut.4c00203\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/8/6 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Pharmaceutics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1021/acs.molpharmaceut.4c00203","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/6 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Construction of a Multifunctional Upconversion Nanoplatform Based on Autophagy Inhibition and Photodynamic Therapy Combined with Chemotherapy for Antitumor Therapy.
Inhibition of autophagy increases the sensitivity of tumor cells to radiotherapy and chemotherapy and improves the therapeutic effect on tumors. Recently, photodynamic therapy (PDT) combined with chemotherapy has been proven to further improve the efficiency of cancer treatment. As such, combining autophagy inhibition with PDT and chemotherapy may represent a potentially effective new strategy for cancer treatment. However, currently widely studied autophagy inhibitors inevitably produce various toxic side effects due to their inherent pharmacological activity. To overcome this constraint, in this study, we designed an ideal multifunctional upconversion nanoplatform, UCNP-Ce6-EPI@mPPA + NIR (MUCEN). Control, UCNP-EPI@mPPA (MUE), UCNP-EPI@mPPA + NIR (MUEN), Ce6-EPI@mPPA (MCE), Ce6-EPI@mPPA + NIR (MCEN), and UCNP-Ce6-EPI@mPPA (MUCE) groups were set up separately as controls. Based on a combination of autophagy inhibition and PDT, the average particle size of MUCEN was 197 nm, which can simultaneously achieve the double encapsulation of chlorine e6 (Ce6) and epirubicin (EPI). In vitro tests revealed that MUCE was efficiently endocytosed by 4T1 cells under near-infrared light irradiation. Further, in vivo tests revealed that MUCE dramatically inhibited tumor growth. Immunohistochemistry results indicated that MUCE efficiently increased the expression of autophagy inhibitors p62 and LC3 in tumor tissues. The synergistic effect of autophagy inhibition and PDT with MUCE exhibited superior tumor suppression, providing an innovative approach to cancer treatment.
期刊介绍:
Molecular Pharmaceutics publishes the results of original research that contributes significantly to the molecular mechanistic understanding of drug delivery and drug delivery systems. The journal encourages contributions describing research at the interface of drug discovery and drug development.
Scientific areas within the scope of the journal include physical and pharmaceutical chemistry, biochemistry and biophysics, molecular and cellular biology, and polymer and materials science as they relate to drug and drug delivery system efficacy. Mechanistic Drug Delivery and Drug Targeting research on modulating activity and efficacy of a drug or drug product is within the scope of Molecular Pharmaceutics. Theoretical and experimental peer-reviewed research articles, communications, reviews, and perspectives are welcomed.