Wang Yupeng, Wang Lina, Li Tao, Ouyang Min, Xiong Hejian, Zhou Dongfang
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.
Acta Pharm Sin B. 2024 Apr;14(4):1787-1800. doi: 10.1016/j.apsb.2023.11.028. Epub 2023 Nov 30.
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. However, the safety and efficacy of radio-immunotherapy is impeded by the radio-resistance and poor immunogenicity 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 Fe 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 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 rechallenging is observed. Overall, the bimetallic NPs-based cascade sensitizing amplifier system offers an efficient radio-immunotherapy regimen that addresses the key challenges.
放射疗法（RT）是治疗恶性肿瘤最可行且常用的治疗方式之一。特别是，由RT引发的免疫反应，即放射免疫疗法，可部分抑制远处扩散肿瘤和复发性肿瘤的生长。然而，肿瘤的放射抗性和低免疫原性阻碍了放射免疫疗法的安全性和有效性。在此，我们报道了奥沙利铂（IV）-铁双金属纳米颗粒（OXA/Fe NPs）作为低剂量强效放射免疫疗法的级联增敏放大器。OXA/Fe NPs在肿瘤细胞内的还原和酸性微环境作用下表现出肿瘤特异性积累以及OXA（II）和Fe的激活。释放的金属药物的级联反应可通过诱导DNA损伤、增加ROS和O水平以及放大RT后的免疫原性细胞死亡（ICD）效应来使RT增敏，从而促进有效的免疫激活。结果，基于OXA/Fe NPs的低剂量RT引发了强烈的免疫反应，并通过强大的远隔效应有效地抑制了远处和转移性肿瘤。此外，还观察到长期免疫记忆效应可保护小鼠免受肿瘤再次攻击。总体而言，基于双金属纳米颗粒的级联增敏放大器系统提供了一种有效的放射免疫疗法方案，解决了关键挑战。
