恶性黑色素瘤是一种侵袭性皮肤癌，具有高转移率和死亡率。由于基因改变，黑色素瘤细胞对细胞凋亡诱导具有抵抗力，这降低了临床上大多数辅助全身抗癌治疗的疗效。在这里，我们提供了一种基于锰配位纳米药物的抗黑色素瘤免疫治疗的无创策略。辅以光照射，光敏剂二氢卟酚 e6 (Ce6) 产生光子介导的活性氧 (ROS)，引发光子控制的细胞焦亡激活 (PhotoPyro) 并促进抗肿瘤免疫。同时，光照射触发的细胞质中双链DNA（dsDNA）的生成将激活Mn2敏化环GMP-AMP合酶（cGAS）-干扰素基因刺激剂（STING）途径，进一步增强PhotoPyro诱导的免疫反应。这些免疫刺激途径的同源效应通过损伤相关分子模式（DAMP）和促炎细胞因子的分泌显着有利于树突状细胞的成熟，从而激活T细胞并显着引发全身抗肿瘤免疫反应以抑制原发性和远处肿瘤的生长。通过纳米药物管理，光照射触发的 PhotoPyro 和 cGAS-STING 通路激活可以增强免疫疗法的抗肿瘤能力，并作为黑色素瘤治疗的一种有前途的策略。本文受版权保护。保留所有权利。本文受版权保护。版权所有。

Malignant melanoma is an aggressive skin cancer with high metastatic and mortality rate. Owing to genetic alterations, melanoma cells are resistant to apoptosis induction, which reduces the efficacy of most adjuvant systemic anticancer treatments in clinical. Here, we provided a noninvasive strategy for anti-melanoma immunotherapy based on a manganese-coordinated nanomedicine. Supplemented with photoirradiation, photon-mediated reactive oxygen species (ROS) generation by photosensitizer chlorin e6 (Ce6) initiated photon-controlled pyroptosis activation (PhotoPyro) and promoted antitumor immunity. Simultaneously, photoirradiation-triggered double-stranded DNA (dsDNA) generation in the cytosol would activate the Mn2+ -sensitized cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, which further augmented the PhotoPyro-induced immune response. The syngeneic effect of these immunostimulatory pathways significantly benefited dendritic cell maturation by damage-associated molecular patterns (DAMPs) and proinflammatory cytokines secretion, thereby activating T cells and remarkably eliciting systemic antitumor immune response to inhibit both primary and distant tumor growth. Collaboratively, the photoirradiation-triggered PhotoPyro and cGAS-STING pathway activation by nanomedicine administration could enhance the antitumor capacity of immunotherapy and serve as a promising strategy for melanoma treatment. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.