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

Acta Pharmaceutica Sinica B 2024年第4期14卷 1787-1800页

作者： Yupeng Wang Lina Wang Tao Li Min Ouyang Hejian Xiong Dongfang Zhou Department of Ultrasonic Diagnosis Zhujiang 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 Center Hebei Normal UniversityShijiazhuang 050024China Department of Mechanical Engineering The University of Texas at DallasRichardsonTX 75080USA

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

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