Light-controllable charge-reversal nanoparticles with polyinosinic-polycytidylic acid for enhancing immunotherapy of triple negative breast cancer.
10.1016/j.apsb.2021.06.006
- Author:
Lei FANG
1
;
Zitong ZHAO
2
;
Jue WANG
2
;
Ping XIAO
2
;
Xiangshi SUN
2
;
Yaping DING
1
;
Pengcheng ZHANG
2
;
Dangge WANG
2
;
Yaping LI
2
Author Information
1. Collage of Sciences, Shanghai University, Shanghai 200444, China.
2. State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
- Publication Type:Journal Article
- Keywords:
Cancer immunotherapy;
Charge-reversal;
Nanoparticles;
Photodynamic therapy;
Polyinosinic-polycytidylic acid;
ROS-responsive;
Triple negative breast cancer;
Tumor microenvironment
- From:
Acta Pharmaceutica Sinica B
2022;12(1):353-363
- CountryChina
- Language:English
-
Abstract:
Nucleic acid drugs are highly applicable for cancer immunotherapy with promising therapeutic effects, while targeting delivery of these drugs to disease lesions remains challenging. Cationic polymeric nanoparticles have paved the way for efficient delivery of nucleic acid drugs, and achieved stimuli-responsive disassembly in tumor microenvironment (TME). However, TME is highly heterogeneous between individuals, and most nanocarriers lack active-control over the release of loaded nucleic acid drugs, which will definitely reduce the therapeutic efficacy. Herein, we have developed a light-controllable charge-reversal nanoparticle (LCCN) with controlled release of polyinosinic-polycytidylic acid [Poly(I:C)] to treat triple negative breast cancer (TNBC) by enhanced photodynamic immunotherapy. The nanoparticles keep suitably positive charge for stable loading of Poly(I:C), while rapidly reverse to negative charge after near-infrared light irradiation to release Poly(I:C). LCCN-Poly(I:C) nanoparticles trigger effective phototoxicity and immunogenic cell death on 4T1 tumor cells, elevate antitumor immune responses and inhibit the growth of primary and abscopal 4T1 tumors in mice. The approach provides a promising strategy for controlled release of various nucleic acid-based immune modulators, which may enhance the efficacy of photodynamic immunotherapy against TNBC.
