二硫仑
螯合作用
化学
体内
羟基自由基
激进的
两亲性
纳米颗粒
癌症研究
细胞毒性T细胞
药理学
体外
材料科学
生物物理学
生物化学
纳米技术
医学
有机化学
共聚物
生物
生物技术
聚合物
作者
Yidan Sun,Chunyue An,Luyan Wu,Wenhui Zeng,Jiafeng Wang,Yanfeng Wang,Jian He,Guandao Gao,Deju Ye
出处
期刊:ACS Nano
[American Chemical Society]
日期:2021-09-30
卷期号:15 (10): 16298-16313
被引量:24
标识
DOI:10.1021/acsnano.1c05485
摘要
Ultrasound (US)-activated nanoagents capable of producing cytotoxic species have been promising for the treatment of deep-seated tumors; however, poor tumor uptake and insufficient generation of cytotoxic agents have largely limited their therapeutic efficacy in vivo. Herein, we report a hybrid FeCuS-lipid nanoparticle (AIBA@FeCuS-FeCO) by amphiphilic lipids-assisted emulsion of a free radical initiator (AIBA), a radical-sensitive CO donor (Fe3(CO)12), and radical-degradable FeCuS nanodisks for US-activated synergistic therapy of deep-located orthotopic gastric tumors in living mice. Upon US irradiation, AIBA@FeCuS-FeCO could be degraded and release cytotoxic AIBA radicals, CO, Fe2+, and Cu2+, allowing us to (1) enhance tumor uptake of AIBA@FeCuS-FeCO through CO-mediated vasodilation, (2) promote hydroxyl radical production and induce tumor ferroptosis via intracellular accumulation of Fe2+/Cu2+, and (3) kill tumor cells. Moreover, the subsequent administration of disulfiram (DSF) could further chelate with the liberated Cu2+, yielding toxic bis(N,N-diethyl dithiocarbamato)copper(II) chelates to synergize the therapeutic effect to ablate deep-seated orthotopic gastric tumors.
科研通智能强力驱动
Strongly Powered by AbleSci AI