ZIF-8 coated gold nanospheres: A multi-responsive drug delivery system promoting the killing effect of photothermal therapy against osteosarcoma cells  

作　　者：Miao Lei Weiye Cai Luetao Zou Bin Yu Lin Chen Yang Cao Shanlin Xiang Chao Song Jiandu Lei Wei Jiang Zhenming Hu 

机构地区：[1]Department of Orthopedics,Orthopedic Laboratory of Chongqing Medical University,The First Affiliated Hospital of Chongqing Medical University,No.1 Youyi Road,Chongqing 400010,China [2]The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University,Luzhou 646699,China [3]Department of Orthopedics,The Third Affiliated Hospital of Chongqing Medical University,Chongqing 400010,China [4]Department of Radiology,The First Affiliated Hospital of Chongqing Medical University,No.1 Youyi Road,Chongqing 400010,China [5]Department of Orthopedics,Chongqing University Three Gorges Hospital,Chongqing 404000,China [6]Department of Geriatrics,The Affiliated Hospital of Guizhou Medical University,Guiyang 550025,China [7]Beijing Key Laboratory of Lignocellulosic Chemistry,College of Material Science and Technology,Beijing Forestry University,Beijing 100083,China

出　　处：《Nano Research》2024年第3期1772-1784,共13页纳米研究（英文版）

基　　金：supported by the National Natural Science Foundation of China(No.82002363);Natural Science Foundation of Chongqing,China(No.cstc2020jcyj-msxmX0195).

摘　　要：Photothermal therapy(PTT)has been widely used in the treatment of tumors,but its efficacy is greatly limited by the inability of precise drug delivery and the increase of heat shock proteins(HSPs)caused by high temperature.This article describes a therapeutic strategy to enhance PTT with starvation therapy in conjunction with ferroptosis mechanism.A nanoparticle platform ZIF-8@GA was constructed by wrapping together glucose oxidase(GOX)and gold nanospheres(AuNPs)loaded with dihydroartemisinin(DHA)with zeolitic imidazolate framework-8(ZIF-8).This platform can take advantage of the micro-environment of osteosarcoma(OS)cells,featuring low pH and high reactive oxygen species(ROS),for precision drug delivery.GOX can effectively catalyze glucose to produce gluconic acid and H_(2)O_(2),and DHA can also induce ROS production in OS cells.ROS produced by GOX and DHA can further generate lipid peroxidation(LPO)and lead to ferroptosis of OS cells.At the same time,ROS and LPO produced can inhibit the expression of HSPs,thereby increasing the therapeutic effect of PTT.In vitro experiments show that the nanoparticles are pH and ROS responsive.1μg/mL GOX combined with 0.2μg/mL DHA promotes ferroptosis of OS cells,and increases the killing effect of near-infrared(NIR)on OS cells.Further in vivo experiments showed that the nano drug-delivery platform combined with PTT can effectively inhibit the growth of OS cells.Meanwhile,this study provides a new idea for the treatment of OS with biomaterials combined with various treatment methods.

关 键 词：zeolitic imidazolate framework-8(ZIF-8) gold nanospheres(AuNPs) photothermal therapy(PTT) starvation therapy ferroptosis 

分 类 号：R738.1[医药卫生—肿瘤]