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

Duo, Yanhong; Chen, Zide; Li, Zihuang; Li, Xing; Yao, Yaoqiang; Xu, Tianzhao; Gao, Ge; Luo, Guanghong · Bioact Mater · 2023

basic_science · Level V

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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 <i>Salmonella</i> 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 <i>via</i> 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.