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基于金的聚集诱导发光(AIE)光敏剂的细菌靶向递送与荧光成像引导相结合用于晚期癌症的增强放射免疫治疗。

Combination of bacterial-targeted delivery of gold-based AIEgen radiosensitizer for fluorescence-image-guided enhanced radio-immunotherapy against advanced cancer.

作者信息

Duo Yanhong, Chen Zide, Li Zihuang, Li Xing, Yao Yaoqiang, Xu Tianzhao, Gao Ge, Luo Guanghong

机构信息

Department of Radiation Oncology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, Guangdong, China.

Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, 17177, Sweden.

出版信息

Bioact Mater. 2023 Aug 22;30:200-213. doi: 10.1016/j.bioactmat.2023.05.010. eCollection 2023 Dec.

Abstract

Aggregation-Induced Emission luminogen (AIEgen) possess great potential in enhancing bioimaging-guided radiotherapeutic effects and radioimmunotherapy to improve the therapeutic effects of the tumor with good biosafety. Bacteria as a natural carrier have demonstrated great advantages in tumor targeted delivery and penetration to tumor. Herein, we construct a delivery platform that VNP20009 act as an activated bacteria vector loaded the as-prepared novel AIEgen (TBTP-Au, VNP@TBTP-Au), which showed excellent radio-immunotherapy. VNP@TBTP-Au could target and retain AIEgen at the tumor site and deliver it into tumor cells specially, upon X-ray irradiation, much ROS was generated to induce immunogenic cell death cGAS-STING signaling pathway to evoke immune response, thus achieving efficient radioimmunotherapy of the primary tumor with good biosafety. More importantly, the radioimmunotherapy with VNP@TBTP-Au formatted good abscopal effect that was able to suppress the growth of distant tumor. Our strategy pioneer a novel and simple strategy for the organic combination of bacteria and imaging-guided radiotherapy, and also pave the foundation for the combination with immunotherapy for better therapeutic effects.

摘要

聚集诱导发光发光体(AIEgen)在增强生物成像引导的放射治疗效果和放射免疫治疗以提高肿瘤治疗效果且具有良好生物安全性方面具有巨大潜力。细菌作为天然载体在肿瘤靶向递送和肿瘤穿透方面已展现出巨大优势。在此,我们构建了一个递送平台,其中VNP20009作为一种活化细菌载体负载所制备的新型AIEgen(TBTP-Au,VNP@TBTP-Au),其显示出优异的放射免疫治疗效果。VNP@TBTP-Au能够在肿瘤部位靶向并保留AIEgen,并将其特异性递送至肿瘤细胞,在X射线照射下,会产生大量活性氧以诱导免疫原性细胞死亡并激活cGAS-STING信号通路以引发免疫反应,从而实现对原发性肿瘤的高效放射免疫治疗且具有良好的生物安全性。更重要的是,VNP@TBTP-Au的放射免疫治疗形成了良好的远隔效应,能够抑制远处肿瘤的生长。我们的策略开创了一种新颖且简单的将细菌与成像引导放射治疗有机结合的策略,也为与免疫治疗相结合以获得更好治疗效果奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02c6/10470274/11de9603f951/ga1.jpg

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