Citation: Hongda Zhu, Kai Ma, Rui Ruan, Chaobo Yang, Aqin Yan, Jing Li, Qi Yu, Hongmei Sun, Mingxing Liu, Hongmei Zheng, Jing Gao, Xiaofang Guan, Zhu Dai, Yao Sun. Tumor-targeted self-assembled micelles reducing PD-L1 expression combined with ICIs to enhance chemo-immunotherapy of TNBC[J]. Chinese Chemical Letters, ;2024, 35(2): 108536. doi: 10.1016/j.cclet.2023.108536 shu

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

Hongda Zhu ^{a, 1*,} ,
Kai Ma ^{a, 1} ,
Rui Ruan ^a ,
Chaobo Yang ^a ,
Aqin Yan ^a ,
Jing Li ^b ,
Qi Yu ^{a, c} ,
Hongmei Sun ^a ,
Mingxing Liu ^a ,
Hongmei Zheng ^b ,
Jing Gao ^d ,
Xiaofang Guan ^e ,
Zhu Dai ^{b, *,} ,
Yao Sun ^{c, *,}

a.
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
b.
Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430079, China
c.
National Key Laboratory of Green Pesticide, College of Chemistry, Central China Normal University, Wuhan 430079, China
d.
Key Laboratory of Medical Optics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China
e.
Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science, Ministry of Education, Qingdao University of Science and Technology, Qingdao 266000, China

bszzhuhongda@yeah.net

daizhu_1226@sina.com

sunyaogbasp@ccnu.edu.cn

Received Date: 7 February 2023
Revised Date: 29 April 2023
Accepted Date: 5 May 2023
Available Online: 6 May 2023

Figures(5)

Immune checkpoint inhibitors (ICIs) therapy targeting programmed cell death ligand 1 (PD-L1) and programmed 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 hydrogen 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 microenvironment. The results presented that PMD integrated chemotherapy and immunotherapy to enhance antitumor 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.
- Immunotherapy,
- Tumor-targeted,
- Self-assembled micelles,
- Metformin,
- Reducing PD-L1 expression,
- TNBC
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