Photoimmunotherapy is a promising cancer treatment modality. While potent 1‐e‐ oxidative species are known to induce immunogenic cell death (ICD), they are also associated with unspecific oxidation and collateral tissue damage. This difficulty may be addressed by post‐generation radical reinforcement. Namely, non‐oxidative radicals are first generated and subsequently activated into powerful oxidative radicals to induce ICD. Here, we developed a photo‐triggered molecular donor (NPCD565) of nitrosoperoxycarbonate (ONOOCO2‐), the first of its class to our knowledge, and further evaluated its feasibility for immunotherapy. Upon irradiation of NPCD565 by light within a broad spectral region from ultraviolet to red, ONOOCO2‐ is released along with a bright rhodamine dye (RD565), whose fluorescence is a reliable and convenient build‐in reporter for the localization, kinetics, and dose of ONOOCO2‐ generation. Upon photolysis of NPCD565 in 4T1 cells, damage‐associated molecular patterns (DAMPs) indicative of ICD were observed and confirmed to exhibit immunogenicity by induced maturation of dendritic cells. In vivo studies with a bilateral tumor‐bearing mouse model showcased the potent tumor‐killing capability of NPCD565 of the primary tumors and growth suppression of the distant tumors. This work unveils the potent immunogenicity of ONOOCO2‐, and its donor (NPCD565) has broad potential for photo‐immunotherapy of cancer.

中文翻译：

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用于光免疫治疗的碳笼罗丹明产生亚硝基过氧碳酸酯

光免疫疗法是一种有前途的癌症治疗方式。虽然已知有效的 1-e- 氧化物质会诱导免疫原性细胞死亡 (ICD)，但它们也与非特异性氧化和附带组织损伤有关。这一困难可以通过后代激进强化来解决。即，首先产生非氧化自由基，随后被激活成强大的氧化自由基以诱导ICD。在这里，我们开发了亚硝基过氧碳酸酯（ONOOCO2-）的光触发分子供体（NPCD565），这是我们所知的同类中的第一个，并进一步评估了其免疫治疗的可行性。在从紫外到红光的宽光谱范围内的光照射 NPCD565 时，ONOOCO2- 与明亮的罗丹明染料 (RD565) 一起释放，其荧光是一种可靠且方便的内置报告剂，用于定位、动力学和剂量ONOOCO2一代。在 4T1 细胞中光解 NPCD565 后，观察到指示 ICD 的损伤相关分子模式 (DAMP)，并证实通过诱导树突状细胞成熟而表现出免疫原性。双侧荷瘤小鼠模型的体内研究显示了 NPCD565 对原发肿瘤的强大杀伤能力和对远处肿瘤生长的抑制能力。这项工作揭示了 ONOOCO2- 的强大免疫原性，其供体 (NPCD565) 在癌症光免疫治疗方面具有广泛的潜力。