Injectable Anti-inflammatory Nanofiber Hydrogel to Achieve Systemic Immunotherapy Post Local Administration
Injectable Anti-inflammatory Nanofiber Hydrogel to Achieve Systemic Immunotherapy Post Local Administration
复制标题
可注射抗炎纳米纤维水凝胶可实现局部给药后的全身免疫治疗。
DOI：
10.1021/acs.nanolett.0c02684
复制
发表时间：
2020-09-09
期刊：
影响因子：
10.8
通讯作者：
Chen, Qian
中科院分区：
文献类型：
--
作者：
Chen, Muchao;Tan, Yanjun;Chen, Qian
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希望，但诸如低客观反应率和不良反应等局限性仍有待解决。本研究开发了一种由类固醇药物自组装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，这种基于类固醇药物的无载体系统可以将促肿瘤免疫抑制肿瘤微环境（TME）重编程为抗肿瘤的TME；另一方面，它可以作为αPDL1持续释放的储存库，从而协同增强免疫系统。局部注射负载α pdl1的水凝胶，在不经治疗的情况下，对局部肿瘤和腹腔肿瘤均有抑制作用。这项工作提出了一种独特的基于水凝胶的递送系统，使用临床批准的药物，有望提高ICB治疗的客观反应率，并最大限度地减少其全身毒性。
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.