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.

中文翻译：

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用于光动力敏化肿瘤免疫疗法的自送光免疫刺激剂

强烈建议将光敏剂和免疫调节剂自我递送至肿瘤部位，以改善光动力免疫疗法，但仍具有挑战性。在此，开发了用于光动力致敏肿瘤免疫疗法的自递送光免疫刺激剂（称为iPS）。无载体iPS是通过优化纯净氯e6（Ce6）和NLG919之间的非共价相互作用而构建的，从而避免了赋形剂引起的毒性和免疫原性。静脉给药的iPS倾向于被动积累在肿瘤组织上，以进行强大的光动力疗法（PDT），并诱导免疫原性细胞死亡（ICD）级联，从而激活细胞毒性T淋巴细胞（CTL）并启动抗肿瘤免疫反应。同时，NLG919的伴随递送抑制了吲哚胺2的活化 3-dioxygenase 1（IDO-1）可逆转免疫抑制性肿瘤微环境。最终，采用iPS的光动力敏化免疫疗法可有效抑制原发性和远处的肿瘤生长，且系统毒性低，这将为开发用于肿瘤精密治疗的临床转化的自递送纳米药物提供启示。