Macrophage-camouflaged epigenetic nanoinducers enhance chemoimmunotherapy in triple negative breast cancer.
10.1016/j.apsb.2022.11.018
- Author:
Tong GAO
1
;
Xiao SANG
1
;
Xinyan HUANG
1
;
Panpan GU
1
;
Jie LIU
1
;
Yongjun LIU
1
;
Na ZHANG
1
Author Information
1. Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
- Publication Type:Journal Article
- Keywords:
Anti-tumor immunity;
Chemoimmunotherapy;
Combination therapy;
Decitabine;
Demethylation;
Epigenetics;
Immunogenic cell death;
Triple negative breast cancer
- From:
Acta Pharmaceutica Sinica B
2023;13(10):4305-4317
- CountryChina
- Language:English
-
Abstract:
Chemoimmunotherapy has been approved as standard treatment for triple-negative breast cancer (TNBC), but the clinical outcomes remain unsatisfied. Abnormal epigenetic regulation is associated with acquired drug resistance and T cell exhaustion, which is a critical factor for the poor response to chemoimmunotherapy in TNBC. Herein, macrophage-camouflaged nanoinducers co-loaded with paclitaxel (PTX) and decitabine (DAC) (P/D-mMSNs) were prepared in combination with PD-1 blockade therapy, hoping to improve the efficacy of chemoimmunotherapy through the demethylation of tumor tissue. Camouflage of macrophage vesicle confers P/D-mMSNs with tumor-homing properties. First, DAC can achieve demethylation of tumor tissue and enhance the sensitivity of tumor cells to PTX. Subsequently, PTX induces immunogenic death of tumor cells, promotes phagocytosis of dead cells by dendritic cells, and recruits cytotoxic T cells to infiltrate tumors. Finally, DAC reverses T cell depletion and facilitates immune checkpoint blockade therapy. P/D-mMSNs may be a promising candidate for future drug delivery design and cancer combination therapy in TNBC.
