Bimetallic nanoparticles as cascade sensitizing amplifiers for low-dose and robust cancer radio-immunotherapy  

作　　者：Yupeng Wang Lina Wang Tao Li Min Ouyang Hejian Xiong Dongfang Zhou 

机构地区：[1]Department of Ultrasonic Diagnosis,Zhujiang Hospital,Key Laboratory of Mental Health of the Ministry of Education,NMPA Key Laboratory for Research and Evaluation of Drug Metabolism&Guangdong Provincial Key Laboratory of New Drug Screening,School of Pharmaceutical Sciences,Southern Medical University,Guangzhou 510515,China [2]Testing and Analysis Center,Hebei Normal University,Shijiazhuang 050024,China [3]Department of Mechanical Engineering,The University of Texas at Dallas,Richardson,TX 75080,USA

出　　处：《Acta Pharmaceutica Sinica B》2024年第4期1787-1800,共14页药学学报（英文版）

基　　金：This work is supported by grants from the National Natural Science Foundation of China(Nos.22275081,and 82372117);Guangdong Basic and Applied Basic Research Foundation(2021B1515120065,China);Guangzhou Science and Technology Bureau(202206010068);the Natural Science Foundation of Hebei Province(E2023205004,China);China Postdoctoral Science Foundation(2022M711532 and 2022T150302).

摘　　要：Radiotherapy(RT)is one of the most feasible and routinely used therapeutic modalities for treating malignant tumors.In particular,immune responses triggered by RT,known as radio-immunotherapy,can partially inhibit the growth of distantly spreading tumors and recurrent tumors.How-ever,the safety and efficacy of radio-immunotherapy is impeded by the radio-resistance and poor immu-nogenicity of tumor.Herein,we report oxaliplatin(IV)-iron bimetallic nanoparticles(OXA/Fe NPs)as cascade sensitizing amplifiers for low-dose and robust radio-immunotherapy.The OXA/Fe NPs exhibit tumor-specific accumulation and activation of OXA(I)and Fe^(2+)in response to the reductive and acidic microenvironment within tumor cells.The cascade reactions of the released metallic drugs can sensitize RT by inducing DNA damage,increasing ROS and O_(2) levels,and amplifying the immunogenic cell death(ICD)effect after RT to facilitate potent immune activation.As a result,OXA/Fe NPs-based low-dose RT triggered a robust immune response and inhibited the distant and metastatic tumors effectively by a strong abscopal effect.Moreover,a long-term immunological memory effect to protect mice from tumor rechal-lenging is observed.Overall,the bimetallic NPs-based cascade sensitizing amplifier system offers an effi-cient radio-immunotherapy regimen that addresses the key challenges.

关 键 词：Bimetallic nanoparticles Radio-immunotherapy Cascade sensitizing amplifier Oxaliplatin Fenton-typeHaber-Weiss reaction RADIOSENSITIZATION Immunogenic cell death Radio-resistance 

分 类 号：R737.9[医药卫生—肿瘤]