Tumor-targeted self-assembled micelles reducing PD-L1 expression combined with ICIs to enhance chemo-immunotherapy of TNBC

Hongda Zhu ¹Kai Ma ¹Rui Ruan ¹Chaobo Yang ¹Aqin Yan ¹Jing Li ²Qi Yu ³Hongmei Sun ¹Mingxing Liu ¹Hongmei Zheng ²Jing Gao ⁴Xiaofang Guan ⁵Zhu Dai ²Yao Sun⁶

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作者信息

1. Cooperative Innovation Center of Industrial Fermentation(Ministry of Education & Hubei Province),Key Laboratory of Fermentation Engineering(Ministry of Education),National"111"Center for Cellular Regulation and Molecular Pharmaceutics,School of Food and Biological Engineering,Hubei University of Technology,Wuhan 430068,China
2. Hubei Cancer Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430079,China
3. Cooperative Innovation Center of Industrial Fermentation(Ministry of Education & Hubei Province),Key Laboratory of Fermentation Engineering(Ministry of Education),National"111"Center for Cellular Regulation and Molecular Pharmaceutics,School of Food and Biological Engineering,Hubei University of Technology,Wuhan 430068,China;National Key Laboratory of Green Pesticide,College of Chemistry,Central China Normal University,Wuhan 430079,China
4. Key Laboratory of Medical Optics,Suzhou Institute of Biomedical Engineering and Technology,Chinese Academy of Sciences,Suzhou 215163,China
5. Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science,Ministry of Education,Qingdao University of Science and Technology,Qingdao 266000,China
6. National Key Laboratory of Green Pesticide,College of Chemistry,Central China Normal University,Wuhan 430079,China
折叠

Abstract

Immune checkpoint inhibitors(ICls)therapy targeting programmed cell death ligand 1(PD-L1)and pro-grammed death protein 1(PD-1)had exhibited significant clinical benefits for cancer treatment such as triple negative breast cancer(TNBC).However,the relatively low anti-tumor immune response rate and ICIs drug resistance highlight the necessity of developing ICIs combination therapy strategies to improve the anti-tumor effect of immunotherapy.Herein,the immunomodulator epigallocatechin gallate palmitate(PEGCG)and the immunoadjuvant metformin(MET)self-assembled into tumor-targeted micelles via hy-drogen bond and electrostatic interaction,which encapsulated the therapeutic agents doxorubicin(DOX)-loaded PEGCG-MET micelles(PMD)and combined with ICIs(anti-PD-1 antibody)as therapeutic strategy to reduce the endogenous expression of PD-L1 and improve the tumor immunosuppressive microenvi-ronment.The results presented that PMD integrated chemotherapy and immunotherapy to enhance an-titumor efficacy in vitro and in vivo,compared with DOX or anti-PD-1 antibody for the therapy of TNBC.PMD micelles might be a potential candidate,which could remedy the shortcomings of antibody-based ICIs and provide synergistic effect to enhance the antitumor effects of ICIs in tumor therapy.

Key words

Immunotherapy/Tumor-targeted/Self-assembled micelles/Metformin/Reducing PD-L1 expression/TNBC

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基金项目

projects of the National Key Research and Development Program(2021YFA0716702)

国家自然科学基金(61805122)

国家自然科学基金(22022404)

国家自然科学基金(22074050)

Green Industry Science and Technology Leading Project of Hubei University of Technology(XJ2021003301)

湖北省自然科学基金(2022CFA033)

Chinese Society of Clinical Oncology(CSCO)supported by Jiangsu Hengrui Cancer Research Foundation(YHR2019-0325)

中央高校基本科研业务费专项(CCNU22QN007)

Opening Fund from the Jiangsu Key Laboratory of Medical Optics,Suzhou Institute of Biomedical Engineering and Technology(JKLMO202203)

Key Laboratory of Opticelectric Sensing and Analytical Chemistry for Life Science,MO(M2022-5)

出版年

2024

中国化学快报(英文版)

中国化学会

中国化学快报(英文版)

CSTPCDCSCD

影响因子：0.771

ISSN：1001-8417

参考文献量46

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