Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, 199 Ren'ai Road, Suzhou 215123, Jiangsu, P.R. China.
Nano Lett. 2020 Sep 9;20(9):6763-6773. doi: 10.1021/acs.nanolett.0c02684. Epub 2020 Aug 11.
Despite the great promise achieved by immune checkpoint blockade (ICB) therapy in harnessing the immune system to combat different tumors, limitations such as low objective response rates and adverse effects remain to be resolved. Here, an anti-inflammatory nanofiber hydrogel self-assembled by steroid drugs is developed for local delivery of antiprogrammed cell death protein ligand 1 (αPDL1). Interestingly, on the one hand this carrier-free system based on steroid drugs can reprogram the pro-tumoral immunosuppressive tumor microenvironment (TME) to antitumoral TME; on the other hand, it would serve as a reservoir for sustained release of αPDL1 so as to synergistically boost the immune system. By local injection of such αPDL1-loaded hydrogel, effective therapeutic effects were observed in inhibiting both local tumors and abscopal tumors without any treatment. This work presents a unique hydrogel-based delivery system using clinically approved drugs, showing promise in improving the objective response rate of ICB therapy and minimizing its systemic toxicity.
尽管免疫检查点阻断 (ICB) 疗法在利用免疫系统对抗不同肿瘤方面取得了巨大的进展，但仍存在一些限制，如客观反应率低和不良反应等问题有待解决。在这里，开发了一种由甾体药物自组装而成的抗炎纳米纤维水凝胶，用于局部递送抗程序性细胞死亡蛋白配体 1（αPDL1）。有趣的是，一方面，这种基于甾体药物的无载体系统可以重新编程促肿瘤免疫抑制肿瘤微环境 (TME) 为抗肿瘤 TME；另一方面，它可以作为 αPDL1 的持续释放储库，从而协同增强免疫系统。通过局部注射这种负载 αPDL1 的水凝胶，观察到在没有任何治疗的情况下，有效抑制了局部肿瘤和远隔肿瘤的治疗效果。这项工作提出了一种使用临床批准药物的独特水凝胶递送系统，有望提高 ICB 治疗的客观反应率，并最小化其系统毒性。
