癌症研究
肿瘤微环境
光动力疗法
免疫疗法
黑色素瘤
转移
细胞毒性T细胞
免疫系统
免疫原性细胞死亡
肿瘤缺氧
免疫检查点
医学
化学
免疫学
癌症
内科学
放射治疗
体外
生物化学
有机化学
作者
Xin Zheng,Yi Shi,Dongsheng Tang,Haihua Xiao,Kun Shang,Xuezhi Zhou,Guoliang Tan
标识
DOI:10.1002/advs.202206932
摘要
Abstract 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.
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