Localized light-triggered release macrophage cytopharmaceuticals containing <i>O</i>-nitrobenzyl group for enhanced solid tumor cell-chemotherapy.

Jinhu LIU; Han YANG; Xiao SANG; Tong GAO; Zipeng ZHANG; Shunli FU; Huizhen YANG; Lili CHANG; Xiaoqing LIU; Shuang LIANG; Shijun YUAN; Suyun WEI; Yuxin YANG; Xiaoxin YAN; Xinke ZHANG; Weiwei MU; Yongjun LIU; Na ZHANG

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Localized light-triggered release macrophage cytopharmaceuticals containing O-nitrobenzyl group for enhanced solid tumor cell-chemotherapy.

Author: Jinhu LIU ¹ ; Han YANG ¹ ; Xiao SANG ¹ ; Tong GAO ¹ ; Zipeng ZHANG ¹ ; Shunli FU ¹ ; Huizhen YANG ¹ ; Lili CHANG ¹ ; Xiaoqing LIU ¹ ; Shuang LIANG ¹ ; Shijun YUAN ¹ ; Suyun WEI ¹ ; Yuxin YANG ¹ ; Xiaoxin YAN ¹ ; Xinke ZHANG ¹ ; Weiwei MU 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: Cell-chemotherapy; Cytopharmaceutical; Exosome; Light-triggered release; Macrophage; O-Nitrobenzyl; Solid tumor; Upconverting nanoparticle
From: Acta Pharmaceutica Sinica B 2024;14(11):5053-5068
CountryChina
Language:English
Abstract: Cytopharmaceutical based on macrophages is a breakthrough in the field of targeted drug delivery. However, it remains a challenge to localize and control drug release while retaining macrophage activity and exerting its immunotherapeutic effect. Herein, a localized light-triggered release macrophage cytopharmaceutical (USIP@M) was proposed, which could utilize the tumor targeting and immunotherapy effects of macrophages to reverse the immune suppression of tumor microenvironment (TME). Amphiphilic block copolymers with ultraviolet (UV)-responsive o-nitrobenzyl groups were synthesized and co-loaded with sorafenib (SF), IMD-0354 (IMD), and upconverting nanoparticles (UCNPs), which were then taken up by macrophages, and the targeted delivery of drugs was realized by using the tumor tropism of macrophages. UCNPs converted near-infrared light with strong penetrability and high safety into UV light, which promoted the photoresponsive depolymerization of block copolymers and production of exosomes from USIP@M, accelerated drug efflux and maintained the activity of macrophages. IMD simultaneously polarized carrier macrophages and tumor-associated macrophages to exert the antitumor effect of macrophages, enhance T cell immunity, and alleviate the immunosuppressive state of TME. Synergistically with the chemotherapeutic effect of SF, it could effectively kill tumors. In conclusion, based on the localized light-triggered release strategy, this study constructed a novel macrophage cytopharmaceutical that could localize and control drug release while retaining the activity of macrophages and exerting its immunotherapeutic effect, which could effectively treat solid tumors.