Cell relay-delivery improves targeting and therapeutic efficacy in tumors  

作　　者：Ye Feng Qianqian Liu Yi Li Yang Han Meng Liang Hao Wang Qing Yao Yuli Wang Meiyan Yang Zhiping Li Wei Gong Yang Yang Chunsheng Gao 

机构地区：[1]State Key Laboratory of Toxicology and Medical Countermeasures,Beijing Institute of Pharmacology and Toxicology,Beijing,100850,PR China [2]Hubei University of Science and Technology,Xianning,437100,PR China [3]School of Traditional Chinese Medicine,Shenyang Pharmaceutical University,Shenyang,110016,PR China

出　　处：《Bioactive Materials》2021年第6期1528-1540,共13页生物活性材料（英文）

基　　金：We are grateful for the financial support from National Natural Science Foundation of China(No.82073783);National Science and Technology Major Projects for“Major New Drugs Innovation and Development”(Grant No.2018ZX09711003-008-001).

摘　　要：Cell-mediated drug delivery system(CDDS)has shown great potential for cancer therapy.However,a single cell-mediated drug delivery mechanism has not generally been successful,particularly for systemic administration.To augment the antitumor therapy efficacy,herein,we propose a strategy of cell relay-delivery for the use of artificially damaging/aging erythrocytes to hitchhike on circulating monocytes/macrophages for intratumoral accumulation of anticancer drugs.This biomimetic relay-delivery strategy was derived from the manner in which circulating monocytes/macrophages in body specifically engulf damaged/senescent erythrocytes and actively transmigrate into the tumor bulk.The strategy elegantly combines the natural functions of both cells,which therefore provides a new perspective to challenge current obstacles in drug delivery.According to the strategy,we developed biotinylated erythrocyte-poly(lactic-co-glycolic acid)(PLGA)nanoparticle hybrid DDSs(bE-NPs)using avidin-biotin coupling.In such a system,biotinylated erythrocytes can mimic the natural property of damaged/senescent erythrocytes,while PLGA NPs are capable of encapsulating anticancer drugs and promoting sustained drug release.Anticancer drugs can effectively target tumor sites by two steps.First,by using biotinylated erythrocytes as the carrier,the drug-loaded PLGA NPs could be specifically phagocytized by monocytes/macrophages.Second,by taking advantage of the tumor-tropic property of monocytes/macrophages,the drug-loaded PLGA NPs could be efficiently transported into the tumor bulk.After encapsulating vincristine(VIN)as the model drug,bE-NPs exhibited the most favorable antitumor effects in vitro and in vivo by the cell relay-delivery effect.These results demonstrate that the cell relay-delivery provides a potential method for improving tumor treatment efficacy.

关 键 词：Cell relay-delivering Cell-mediated drug delivery HITCHHIKING Solid tumor 

分 类 号：R73[医药卫生—肿瘤] R318[医药卫生—临床医学]