Self-propelled nanomotor reconstructs tumor microenvironment through synergistic hypoxia alleviation and glycolysis inhibition for promoted anti-metastasis.
10.1016/j.apsb.2021.04.006
- Author:
Wenqi YU
1
;
Ruyi LIN
1
;
Xueqin HE
1
;
Xiaotong YANG
1
;
Huilin ZHANG
1
;
Chuan HU
1
;
Rui LIU
1
;
Yuan HUANG
1
;
Yi QIN
2
;
Huile GAO
1
Author Information
1. Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
2. Department of Orthopedics, Zhuhai Hospital, Jinan University, Zhuhai People's Hospital, Guangdong 519000, China.
- Publication Type:Journal Article
- Keywords:
Aerobic glycolysis;
Anti-metastasis;
Chemotherapy;
Enzyme-powered;
Hypoxia;
Microenvironment modulation;
Nanomotor;
Triple negative breast cancer
- From:
Acta Pharmaceutica Sinica B
2021;11(9):2924-2936
- CountryChina
- Language:English
-
Abstract:
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 effect" compromise 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
