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用于癌症免疫光疗的具有免疫检查点抑制作用的明矾调节型透明质酸基水凝胶。

Alum-tuned hyaluronic acid-based hydrogel with immune checkpoint inhibition for immunophoto therapy of cancer.

作者信息

Kim Sungyun, Ahn Jae-Hee, Jeong Da In, Yang Mingyu, Jeong Jae-Hyeon, Choi Yeoung Eun, Kim Hyun Jin, Han Youngjoo, Karmakar Mrinmoy, Ko Hyun-Jeong, Cho Hyun-Jong

机构信息

Department of Pharmacy, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea.

Department of Pharmacy, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea; Kangwon Institute of Inclusive Technology, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea.

出版信息

J Control Release. 2023 Oct;362:1-18. doi: 10.1016/j.jconrel.2023.08.027. Epub 2023 Aug 24.

Abstract

Alum-crosslinked hyaluronic acid-dopamine (HD) hydrogel containing indocyanine green (ICG) with anti-programmed cell death-1 (PD-1) antibody (Ab) administration was developed for immunophoto therapy of cancer. Alum modulates the rheological characteristics of hydrogel for enabling syringe injection, shear-thinning feature, and slower biodegradation. In addition, alum in HD-based hydrogel provided CD8 T cell-mediated immune responses for cancer therapy. ICG in the hydrogel under near-infrared (NIR) light exposure may induce hyperthermia and generate singlet oxygen for selective cancer cell killing. HD/alum/ICG hydrogel injection with NIR laser irradiation elevated PD-1 level in CD8 T cells. Administration of PD-1 Ab aiming at highly expressed PD-1 in T cells may amplify the anticancer efficacies of HD/alum/ICG hydrogel along with NIR laser. HD/alum/ICG hydrogel with NIR light may have both CD8 T cell-linked immune responses and ICG-related photodynamic/photothermal effects. Additional injection of immune checkpoint inhibitor can ultimately suppress primary and distant tumor growth by combination with those therapeutic actions.

摘要

开发了一种含有吲哚菁绿(ICG)的明矾交联透明质酸-多巴胺(HD)水凝胶,并给予抗程序性细胞死亡蛋白1(PD-1)抗体(Ab)用于癌症的免疫光疗。明矾调节水凝胶的流变学特性,以实现注射器注射、剪切变稀特性和较慢的生物降解。此外,基于HD的水凝胶中的明矾为癌症治疗提供了CD8 T细胞介导的免疫反应。水凝胶中的ICG在近红外(NIR)光照射下可能会诱导热疗并产生单线态氧以选择性杀死癌细胞。HD/明矾/ICG水凝胶注射并结合近红外激光照射可提高CD8 T细胞中的PD-1水平。针对T细胞中高表达的PD-1给予PD-1 Ab可能会增强HD/明矾/ICG水凝胶与近红外激光联合的抗癌效果。具有近红外光的HD/明矾/ICG水凝胶可能同时具有与CD8 T细胞相关的免疫反应和与ICG相关的光动力/光热效应。额外注射免疫检查点抑制剂最终可通过与这些治疗作用相结合来抑制原发性和远处肿瘤的生长。

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