Bimetallic nanoparticles as cascade sensitizing amplifiers for low-dose and robust cancer radio-immunotherapy
作者机构：Department of Ultrasonic DiagnosisZhujiang HospitalKey Laboratory of Mental Health of the Ministry of EducationNMPA Key Laboratory for Research and Evaluation of Drug Metabolism&Guangdong Provincial Key Laboratory of New Drug ScreeningSchool of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Testing and Analysis CenterHebei Normal UniversityShijiazhuang 050024China Department of Mechanical EngineeringThe University of Texas at DallasRichardsonTX 75080USA
出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)
年 卷 期：2024年第14卷第4期
页 面：1787-1800页
核心收录：
学科分类：1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
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).
主 题：Bimetallic nanoparticles Radio-immunotherapy Cascade sensitizing amplifier,Oxaliplatin Fenton-typeHaber-Weiss reaction Radiosensitization Immunogenic cell death Radio-resistance
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.
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