Self-propelled nanomotor reconstructs tumor microenvironment through synergistic hypoxia alleviation and glycolysis inhibition for promoted anti-metastasis

作     者：Wenqi Yu Ruyi Lin Xueqin He Xiaotong Yang Huilin Zhang Chuan Hu Rui Liu Yuan Huang Yi Qin Huile Gao Wenqi Yu;Ruyi Lin;Xueqin He;Xiaotong Yang;Huilin Zhang;Chuan Hu;Rui Liu;Yuan Huang;Yi Qin;Huile Gao

作者机构：Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China Department of OrthopedicsZhuhai HospitalJinan UniversityZhuhai People’s HospitalGuangdong 519000China 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2021年第11卷第9期

页      面：2924-2936页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by National Natural Science Foundation of China(No.81961138009) the Fundamental Research Funds for the Central Universities(Nos.SCU2017A001,2018SCUH0024,China) 111 Project(No.B18035,China) the Key Research and Development Program of Science and Technology Department of Sichuan Province(No.2020YFS0570,China) 

主　　题：Nanomotor Microenvironment modulation Hypoxia Aerobic glycolysis Triple negative breast cancer Anti-metastasis Enzyme-powered Chemotherapy 

摘      要：Solid tumors always exhibit local hypoxia,resulting in the high metastasis and inertness to chemotherapy.Reconstruction of hypoxic tumor microenvironment(TME)is considered a potential therapy compared to directly killing tumor cells.However,the insufficient oxygen delivery to deep tumor and the confronting Warburg effectcompromise the efficacy of hypoxia alleviation.Herein,we construct a cascade enzyme-powered nanomotor(NM-si),which can simultaneously provide sufficient oxygen in deep tumor and inhibit the aerobic glycolysis to potentiate anti-metastasis in chemotherapy.Catalase(Cat)and glucose oxidase(GOx)are co-adsorbed on our previously reported CAuNCs@HA to form self-propelled nanomotor(NM),with hexokinase-2(HK-2)siRNA further condensed(NM-si).The persistent production of oxygen bubbles from the cascade enzymatic reaction propels NM-si to move forward autonomously and in a controllable direction along H_(2)O_(2) gradient towards deep tumor,with hypoxia successfully alleviated in the meantime.The autonomous movement also facilitates NM-si with lysosome escaping for efficient HK-2 knockdown to inhibit glycolysis.In vivo results demonstrated a promising anti-metastasis effect of commercially available albumin-bound paclitaxel(PTX@HSA)after pre-treated with NM-si for TME reconstruction.This cascade enzyme-powered nanomotor provides a potential prospect in reversing the hypoxic TME and metabolic pathway for reinforced anti-metastasis of chemotherapy.