A Mitochondria-Targeted NIR-II AIEgen Induced Pyroptosis for Enhanced Tumor Immunotherapy

Cancer immunotherapy is a favorable strategy for facilitating anti-tumor immunity, but it shows limited benefits in clinical practice owing to the immunosuppressive tumor microenvironment. Pyroptosis shows great immunostimulatory effect on tumor, whereas the lack of pyroptotic inducer with imaging property has restricted its progress in tumor theranostics. Herein, a mitochondria-targeted aggregation-induced emission (AIE) luminogen (TPA-2TIN) with NIR-II emission is designed for highly efficient induction of tumor cell pyroptosis. The fabricated TPA-2TIN nanoparticles can be efficiently taken up by tumor cells and selectively accumulated in tumor for a long term observed by NIR-II fluorescence imaging. More importantly, the TPA-2TIN nanoparticles can effectively stimulate immune responses both in vitro and in vivo mediated by the mitochondrial dysfunctions and the subsequent activation of the pyroptotic pathway. Ultimately, the reversal of the immunosuppressive tumor microenvironment significantly enhances the immune checkpoint therapy. This study paves a new avenue for adjuvant immunotherapy of cancer.

Automated summary

Cancer immunotherapy is hindered by the immunosuppressive tumor microenvironment, but a new study presents a mitochondria-targeted AIE luminogen that can effectively induce tumor cell pyroptosis and enhance immune responses. The nanoparticles designed for this purpose were successfully taken up by tumor cells and accumulated in the tumor for long-term monitoring. The activation of the pyroptotic pathway reversed the immunosuppressive tumor microenvironment and improved the efficacy of immune checkpoint therapy.