Natural killer cell-mimicking nanomaterial for overcoming the multidrug resistance of tumor via cascade catalysis

• Published in: Science China materials Vol. 66; no. 3; pp. 1215 - 1226
• Main Authors: Li, Min-Jie, Gao, Fan, Huang, Qian-Xiao, Feng, Jun, Liu, Chuan-Jun, Gong, Shu-Ling, Zhang, Xian-Zheng
• Format: Journal Article
• Language: English
• Published: Beijing Science China Press 01.03.2023; Springer Nature B.V
• Subjects: Anticancer properties; Biomimetics; Blood circulation; Catalysis; Cell membranes; Chemical synthesis; Chemistry and Materials Science; Chemistry/Food Science; Doxorubicin; Liquid oxygen; Manganese dioxide; Materials Science; Nanomaterials; Nanoparticles; multidrug resistance; Fenton-like reaction; cascade catalysis; natural killer cell
• ISSN: 2095-8226; 2199-4501
• DOI: 10.1007/s40843-022-2205-1

Despite the availability and prosperity of chemotherapeutic agents, multidrug resistance (MDR) remains the paramount obstacle in antitumor chemotherapy. Here, a natural killer (NK) cell-biomimetic nanoparticle (DMLN) is developed to overcome MDR by promoting the entry of doxorubicin (DOX) into tumor cells via cascade catalysis. DMLN is synthesized by compounding the NK cell membrane with hollow MnO 2 nanoparticles loaded with DOX and lactate oxidase (LOX). When it reaches the tumor microenvironment, DMLN can be degraded and release Mn 2+ . A Fenton-like reaction subsequently occurs and generates a large amount of •OH around the tumor cell membrane. •OH will increase the permeability of the tumor plasma membrane for DOX diffusion into the tumor cells. The high concentration of intracellular DOX will overcome the MDR. Owing to the NK cell membrane coating, DMLN can maintain excellent tumor blood circulation and tumor accumulation abilities. In vitro and in vivo experiments have verified the remarkable antitumor effect of DMLN against MDR tumors. This NK cell-mimicking strategy provides a promising modality to overcome MDR for tumor treatment.