Enhancing cancer chemo-immunotherapy by biomimetic nanogel with tumor targeting capacity and rapid drug-releasing in tumor microenvironment  

作　　者：Lihuan Shang Xue Jiang Ting Yang Hongbo Xu Qi Xie Mei Hu Conglian Yang Li Kong Zhiping Zhang 

机构地区：[1]Tongji School of Pharmacy,Huazhong University of Science and Technology,Wuhan 430030,China [2]Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation,Medical Research Center,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510120,China [3]National Engineering Research Center for Nanomedicine,Huazhong University of Science and Technology,Wuhan 430030,China [4]Hubei Engineering Research Centre for Novel Drug Delivery System,Huazhong University of Science and Technology,Wuhan 430030,China

出　　处：《Acta Pharmaceutica Sinica B》2022年第5期2550-2567,共18页药学学报（英文版）

基　　金：supported by National Natural Science Foundation of China (81673374,China);Program for HUST Academic Frontier Youth Team (2018QYTD13,China);Natural Science Foundation of Hubei Province (2020CFB301,China)。

摘　　要：In the development of chemo-immunotherapy, many efforts have been focusing on designing suitable carriers to realize the co-delivery of chemotherapeutic and immunotherapeutic with different physicochemical properties and mechanisms of action. Besides, rapid drug release at the tumor site with minimal drug degradation is also essential to facilitate the antitumor effect in a short time. Here, we reported a cancer cell membrane-coated pH-responsive nanogel(NG@M) to co-deliver chemotherapeutic paclitaxel(PTX) and immunotherapeutic agent interleukin-2(IL-2) under mild conditions for combinational treatment of triple-negative breast cancer. In the designed nanogels, the synthetic copolymer PDEA-co-HP-β-cyclodextrin-co-Pluronic F127 and charge reversible polymer dimethylmaleic anhydride-modified polyethyleneimine endowed nanogels with excellent drug-loading capacity and rapid responsive drug-releasing behavior under acidic tumor microenvironment. Benefited from tumor homologous targeting capacity, NG@M exhibited 4.59-fold higher accumulation at the homologous tumor site than heterologous cancer cell membrane-coated NG. Rapidly released PTX and IL-2 enhanced the maturation of dendritic cells and quickly activated the antitumor immune response in situ, followed by prompted infiltration of immune effector cells. By the combined chemo-immunotherapy, enhanced antitumor effect and efficient pulmonary metastasis inhibition were achieved with a prolonged median survival rate(39 days).

关 键 词：CHEMO-IMMUNOTHERAPY NANOGEL PH-RESPONSIVE Cancer cell membrane BIOMIMETIC 

分 类 号：R943[医药卫生—药剂学]