基于级联催化的仿生NK细胞纳米材料用于克服肿瘤多药耐药  

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

作　　者：李敏捷 高凡 黄千笑 冯俊 刘传军 龚淑玲 张先正 Min-Jie Li;Fan Gao;Qian-Xiao Huang;Jun Feng;Chuan-Jun Liu;Shu-Ling Gong;Xian-Zheng Zhang(Key Laboratory of Biomedical Polymers of Ministry of Education&Department of Chemistry,Wuhan University,Wuhan 430072,China)

机构地区：[1]Key Laboratory of Biomedical Polymers of Ministry of Education&Department of Chemistry,Wuhan University,Wuhan 430072,China

出　　处：《Science China Materials》2023年第3期1215-1226,共12页中国科学（材料科学（英文版）

基　　金：supported by the National Natural Science Foundation of China(52073219,22135005,52131302,and 51833007).

摘　　要：由于优异的治疗效果,化疗被广泛应用于癌症的早期治疗.但在肿瘤化疗过程中,多药耐药(MDR)的出现,成为了抗肿瘤化疗的首要障碍.本文提出了一种仿生自然杀伤(NK)细胞的纳米粒子(DMLN),通过级联催化反应促进阿霉素(DOX)进入肿瘤细胞以克服MDR.DMLN是通过将NK细胞膜与负载有DOX和乳酸氧化酶(LOX)的中空二氧化锰纳米粒子复合来实现的.在肿瘤微环境中,DMLN可以降解并释放Mn2+,然后发生类Fenton反应,在肿瘤细胞周围产生大量羟基自由基(·OH).·OH会增加肿瘤细胞膜的通透性,促进DOX进入肿瘤细胞,进而提高细胞内DOX的浓度以克服MDR.此外,由于NK细胞膜的包覆,DMLN具有良好的肿瘤血液循环和肿瘤聚集能力.体外和体内实验显示,DMLN对多药耐药肿瘤具有显著的抗肿瘤作用.这种NK细胞模拟策略为克服肿瘤治疗中的MDR提供了一种新的思路.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 Mn2+.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 cellmimicking strategy provides a promising modality to overcome MDR for tumor treatment.

关 键 词：肿瘤微环境 肿瘤多药耐药 类FENTON反应 肿瘤化疗 NK细胞 乳酸氧化酶 血液循环 聚集能力 

分 类 号：R730.5[医药卫生—肿瘤] TB383.1[医药卫生—临床医学]