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

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

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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(Ⅱ)and Fe2+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 O2 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.

Bimetallic nanoparticlesRadio-immunotherapyCascade sensitizing amplifierOxaliplatinFenton-type Haber-Weiss reactionRadiosensitizationImmunogenic cell deathRadio-resistance

Yupeng Wang、Lina Wang、Tao Li、Min Ouyang、Hejian Xiong、Dongfang Zhou

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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

Testing and Analysis Center,Hebei Normal University,Shijiazhuang 050024,China

Department of Mechanical Engineering,The University of Texas at Dallas,Richardson,TX 75080,USA

国家自然科学基金国家自然科学基金Guangdong Basic and Applied Basic Research FoundationGuangzhou Science and Technology Bureau河北省自然科学基金中国博士后科学基金中国博士后科学基金

22275081823721172021B1515120065202206010068E20232050042022M7115322022T150302

2024

10.1016/j.apsb.2023.11.028

药学学报(英文版)

药学学报(英文版)

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ISSN：
年,卷(期)：2024.14(4)
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