Self-Delivery Photo-Immune Stimulators for Photodynamic Sensitized Tumor Immunotherapy.

Zhao, Lin-Ping; Zheng, Rong-Rong; Huang, Jia-Qi; Chen, Xia-Yun; Deng, Fu-An; Liu, Yi-Bin; Huang, Chu-Yu; Yu, Xi-Yong et al. · ACS Nano · 2020

basic_science · Level V

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Abstract

Self-delivery of photosensitizer and immune modulator to tumor site is highly recommendable to improve the photodynamic immunotherapy yet remains challenging. Herein, self-delivery photoimmune stimulators (designated as iPSs) are developed for photodynamic sensitized tumor immunotherapy. Carrier-free iPSs are constructed by optimizing the noncovalent interactions between the pure drugs of chlorine e6 (Ce6) and NLG919, which avoid the excipients-raised toxicity and immunogenicity. Intravenously administrated iPSs prefer to passively accumulate on tumor tissues for a robust photodynamic therapy (PDT) with the induction of immunogenetic cell death (ICD) cascade to activate cytotoxic T lymphocytes (CTLs) and initiate antitumor immune response. Meanwhile, the concomitant delivery of NLG919 inhibits the activation of indoleamine 2,3-dioxygenase 1 (IDO-1) to reverse the immunosuppressive tumor microenvironment. Ultimately, the photodynamic sensitized immunotherapy with iPSs efficiently inhibit the primary and distant tumor growth with a low system toxicity, which would shed light on the development of self-delivery nanomedicine for clinical transformation in tumor precision therapy.