光动力疗法（PDT）因其有效性而被广泛应用于肿瘤治疗。然而，血管系统异常引起的肿瘤缺氧微环境严重限制了PDT的疗效。此外，异常的脉管系统与免疫治疗的失败有关。在这项研究中，引入了一种称为Combo-NP的新型纳米粒子，它由主链上具有二硫键的可生物降解的NIR II荧光假共轭聚合物（称为TPA-BD）和血管抑制剂Lenvatinib组成。 Combo-NP 具有双重功能，不仅可以诱导细胞毒性活性氧 (ROS) 直接消除肿瘤细胞，还可以引发免疫原性细胞死亡 (ICD)。这种 ICD 反应反过来会引发一系列强大的免疫反应，从而增加细胞毒性 T 淋巴细胞 (CTL) 的产生。此外，Combo-NP 通过使肿瘤脉管系统正常化来解决肿瘤缺氧问题。这种标准化过程增强了 PDT 的功效，同时促进了肿瘤微环境中 CTL 的浸润增加。这些协同效应协同增强纳米颗粒的光动力免疫治疗特性。此外，当与抗程序性死亡配体1（PD-L1）结合时，它们对肿瘤转移表现出显着的抑制作用。本研究的结果介绍了一种创新的纳米医学策略，旨在触发全身抗肿瘤免疫反应来治疗葡萄膜黑色素瘤。© 2023 作者。 《先进科学》由 Wiley-VCH GmbH 出版。

Photodynamic therapy (PDT) has been widely employed in tumor treatment due to its effectiveness. However, the tumor hypoxic microenvironment which is caused by abnormal vasculature severely limits the efficacy of PDT. Furthermore, the abnormal vasculature has been implicated in the failure of immunotherapy. In this study, a novel nanoparticle denoted as Combo-NP is introduced, composed of a biodegradable NIR II fluorescent pseudo-conjugate polymer featuring disulfide bonds within its main chain, designated as TPA-BD, and the vascular inhibitor Lenvatinib. Combo-NP exhibits dual functionality by not only inducing cytotoxic reactive oxygen species (ROS) to directly eliminate tumor cells but also eliciting immunogenic cell death (ICD). This ICD response, in turn, initiates a robust cascade of immune reactions, thereby augmenting the generation of cytotoxic T lymphocytes (CTLs). In addition, Combo-NP addresses the issue of tumor hypoxia by normalizing the tumor vasculature. This normalization process enhances the efficacy of PDT while concurrently fostering increased CTLs infiltration within the tumor microenvironment. These synergistic effects synergize to potentiate the photodynamic-immunotherapeutic properties of the nanoparticles. Furthermore, when combined with anti-programmed death-ligand 1 (PD-L1), they showcase notable inhibitory effects on tumor metastasis. The findings in this study introduce an innovative nanomedicine strategy aimed at triggering systemic anti-tumor immune responses for the treatment of Uveal melanoma.© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.