Abstract：
Phototherapy promotes anti-tumor immunity by inducing immunogenic cell death (ICD), However, the accompanying inflammatory responses also trigger immunosuppression, attenuating the efficacy of photo-immunotherapy. Herein, they co-assembled a cell-membrane targeting chimeric peptide C16-Cypate-RRKK-PEG8-COOH (CCP) and anti-inflammatory diclofenac (DA) to develop a nanodrug (CCP@DA) that both enhances the immune effect of phototherapy and weakens the inflammation-mediated immunosuppression. CCP@DA achieves cell membrane-targeting photodynamic and photothermal synergistic therapies to damage programmed death ligand 1 (PD-L1) and induce a strong ICD to activate anti-tumor response. Simultaneously, the released DA inhibits the cycoperoxidase-2 (COX-2)/prostaglandin E2 (PGE2) pathway in tumor cells to inhibit pro-tumor inflammation and further down-regulate PD-L1 expression to relieve the immunosuppressive microenvironment. CCP@DA significantly inhibited tumor growth and inflammation both in vitro and in vivo, while maintaining a potent anti-tumor immune response. Additionally, it exhibits excellent anti-metastatic capabilities and prolongs mouse survival time with a single dose and low levels of near-infrared (NIR) light exposure. This work provides a valuable strategy to control the therapy-induced inflammation for high-efficiency photoimmunotherapy.
摘要：
光疗通过诱导免疫原性细胞死亡（ICD）促进抗肿瘤免疫，然而,伴随的炎症反应也会引发免疫抑制，减弱光免疫疗法的疗效。在这里，他们共同组装了靶向细胞膜的嵌合肽C16-Cypate-RRKK-PEG8-COOH（CCP）和抗炎双氯芬酸（DA），以开发一种纳米药物（CCP@DA），该药物既可以增强光疗的免疫效果，又可以减弱炎症介导的免疫抑制。CCP@DA实现了细胞膜靶向光动力和光热协同治疗，以损伤程序性死亡配体1（PD-L1），并诱导强烈的ICD激活抗肿瘤反应。同时,释放的DA抑制肿瘤细胞中的环过氧化物酶-2（COX-2）/前列腺素E2（PGE2）通路以抑制肿瘤炎症，并进一步下调PD-L1表达以缓解免疫抑制微环境。CCP@DA在体外和体内均能显著抑制肿瘤生长和炎症反应，同时保持有效的抗肿瘤免疫反应。此外,它表现出优异的抗转移能力，并通过单剂量和低水平的近红外（NIR）光暴露延长小鼠的存活时间。这项工作为控制高效光免疫疗法的治疗诱导的炎症提供了有价值的策略。
