Nucleic acid drugs are highly applicable for cancer immunotherapy with promising therapeu-tic 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 heteroge-neous 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 immuno-therapy.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)na-noparticles trigger effective phototoxicity and immunogenic cell death on 4T1 tumor cells,elevate anti-tumor 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 mod-ulators,which may enhance the efficacy of photodynamic immunotherapy against TNBC.

Lei Fang;Zitong Zhao;Jue Wang;Ping Xiao;Xiangshi Sun;Yaping Ding;Pengcheng Zhang;Dangge Wang;Yaping Li

Collage of Sciences,Shanghai University,Shanghai 200444,China;State Key Laboratory of Drug Research & Center of Pharmaceutics,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China;Yantai Key Laboratory of Nanomedicine & Advanced Preparations,Yantai Institute of Materia Medica,Yantai 264000,China;School of Pharmacy,Yantai University,Yantai 264005,China

药学学报（英文版）

[1]Lei Fang;Zitong Zhao;Jue Wang;Ping Xiao;Xiangshi Sun;Yaping Ding;Pengcheng Zhang;Dangge Wang;Yaping Li-.Light-controllable charge-reversal nanoparticles with polyinosinic-polycytidylic acid for enhancing immunotherapy of triple negative breast cancer)[J].药学学报（英文版）,2022(01):353-363

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