前药
免疫疗法
癌症免疫疗法
对偶(语法数字)
癌症研究
癌症
免疫原性细胞死亡
医学
药理学
内科学
文学类
艺术
作者
Xiaochun Hu,Ruihao Li,Jie Liu,Kang Fang,Chunyan Dong,Shuo Shi
标识
DOI:10.1002/adhm.202302333
摘要
In recent years, anticancer effects of disulfiram, a clinical drug for anti-alcoholism, have been confirmed. However, several defects limit clinical translation of disulfiram obviously, such as Cu(II)-dependent anticancer activity, instability and non-selectivity for cancer cells. Herein, a phosphate and hydrogen peroxide dual-responsive nanoplatform (PCu-HA-DQ) is reported, which is constructed by encapsulating disulfiram prodrug (DQ) and modifying hyaluronic acid (HA) on copper doping metal-organic frameworks (PCu MOFs). PCu-HA-DQ is expected to accumulate in tumor by targeting CD-44 receptors and enable guidance with magnetic resonance imaging. Inside the tumor, Cu(DTC)2 will be generated in situ based on a dual-responsive reaction. In detail, the high concentration of phosphate could induce the release of DQ, after that, the intracellular hydrogen peroxide would further mediate the generation of Cu(DTC)2 . In vitro and in vivo results indicate PCu-HA-DQ could induce the apoptosis as well as immunogenic cell death (ICD) of tumor cells distinctly, leading to enhanced immune checkpoint inhibitor (ICI) efficacy by combining the anti-programmed death-1 antibody. This work provides a portable strategy to construct dual-responsive nanoplatform integrating tumor-targeted ability and multi-therapy, and the designed nanoplatform is also an ICD inducer, which presents prospect for boosting systemic antitumor immunity and ICI efficacy. This article is protected by copyright. All rights reserved.
科研通智能强力驱动
Strongly Powered by AbleSci AI