Theranostic nanosystem mediating cascade catalytic reactions for effective immunotherapy of highly immunosuppressive and poorly penetrable pancreatic tumor  

作　　者：Gengjia Chen Yujun Cai Bo Li Minzhao Lin Xiaobin Wang Zhiyong Wang Xintao Shuai 

机构地区：[1]Key Laboratory for Polymeric Composite&Functional Materials of Ministry of Education,School of Materials Science and Engineering,Sun Yat-sen University,Guangzhou 510275,China [2]Nanomedicine Research Center,the Third Affiliated Hospital of Sun Yat-sen University,Guangzhou 510630,China [3]Department of Minimally Invasive Interventional Radiology,Laboratory of Interventional Radiology,the Second Affiliated Hospital of Guangzhou Medical University,Guangzhou 510275,China

出　　处：《Science China Chemistry》2022年第7期1383-1400,共18页中国科学（化学英文版）

基　　金：supported by the National Natural Science Foundation of China (51933011, 31971296);the Key Areas Research and Development Program of Guangzhou (202007020006, 2019B020235001);the Natural Science Foundation of the Guangdong Province (2021A1515011799);the Opening Project of State Key Laboratory of Physical Chemistry of Solid Surfaces, Xiamen University (201922);the Science and Technology Project of Yantian District in Shenzhen City, Guangdong Province, China (20190106)。

摘　　要：The dense desmoplastic stroma and immunosuppressive microenvironment of pancreatic cancer hinder the penetration of drugs and induce a considerable resistance to conventional chemoradiotherapy. Although nanomedicine has recently shown attractive potential in cancer immunotherapy, it remains a great challenge to achieve efficient drug delivery and potent immune activation.Here, a stimuli-responsive nanosystem, comprising superparamagnetic iron oxide nanocrystals and nitric oxide(NO) donors,was developed for in-situ triggered catalytic cascade reaction to produce abundant free radicals and remodel the anti-tumor immunity. The nanosystem was activated in the tumor microenvironment to produce NO which dilated the tumor vasculature for efficient drug delivery, and the iron oxide nanocrystals catalyzed the reaction of NO to generate reactive oxygen-nitrogen species(RONS) with high cytotoxicity. Moreover, owing to the catalytic cascade reactions mediated by the nanosystem, the tumor associated macrophages(TAMs) were converted to a proinflammatory M1 phenotype and tumor infiltration of effector T cells was promoted to result in potent anti-tumor immunotherapy which could be readily monitored with magnetic resonance imaging(MRI).

关 键 词：nanozyme catalytic cascade reactions MACROPHAGES tumor microenvironment nitric oxide 

分 类 号：R735.9[医药卫生—肿瘤] TQ460.4[医药卫生—临床医学]