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聚多巴胺纳米粒子交联透明质酸光热水凝胶,具有级联免疫原性效应,用于原位抗肿瘤免疫治疗。

Polydopamine nanoparticles cross-linked hyaluronic acid photothermal hydrogel with cascading immunoinducible effects for in situ antitumor vaccination.

机构信息

Department of Laboratory Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China.

The Affiliated Huai'an Hospital of Xuzhou Medical University and The Second People's Hospital of Huai'an, No. 62, Huaihai Road (S.), Huai'an 223002, China.

出版信息

Int J Biol Macromol. 2024 Jun;269(Pt 2):132177. doi: 10.1016/j.ijbiomac.2024.132177. Epub 2024 May 9.


DOI:10.1016/j.ijbiomac.2024.132177
PMID:38729484
Abstract

Tumor vaccine, which can effectively prevent tumor recurrence and metastasis, is a promising tool in tumor immunotherapy. However, heterogeneity of tumors and the inability to achieve a cascade effect limit the therapeutic effects of most developing tumor vaccine. We have developed a cascading immunoinducible in-situ mannose-functionalized polydopamine loaded with imiquimod phenylboronic hyaluronic acid nanocomposite gel vaccine (M/P-PDA@IQ PHA) through a boronic ester-based reaction. This reaction utilizes mannose-functionalized polydopamine loaded with imiquimod (M/P-PDA@IQ NAs) as a cross-linking agent to react with phenylboronic-grafted hyaluronic acid. Under near-infrared light irradiation, the M/P-PDA@IQ PHA caused local hyperthermia to trigger immunogenic cell death of tumor cells and tumor-associated antigens (TAAs) releasing. Subsequently, the M/P-PDA@IQ NAs which were gradually released by the pH/ROS/GSH-triggered degradation of M/P-PDA@IQ PHA, could capture and deliver these TAAs to lymph nodes. Finally, the M/P-PDA@IQ NAs facilitated maturation and cross-presentation of dendritic cells, as well as activation of cytotoxic T lymphocytes. Overall, the M/P-PDA@IQ PHA could serve as a novel in situ vaccine to stimulate several key nodes including TAAs release and capture, targeting lymph nodes and enhanced dendritic cells uptake and maturation as well as T cells activation. This cascading immune activation strategy can effectively elicit antitumor immune response.

摘要

肿瘤疫苗可有效预防肿瘤的复发和转移,是肿瘤免疫治疗中很有前途的工具。然而,肿瘤的异质性和无法实现级联效应限制了大多数正在开发的肿瘤疫苗的治疗效果。我们通过硼酸酯反应开发了一种级联免疫诱导原位甘露糖功能化载咪喹莫特聚多巴胺负载透明质酸纳米复合凝胶疫苗(M/P-PDA@IQ PHA)。该反应利用甘露糖功能化载咪喹莫特聚多巴胺(M/P-PDA@IQ NAs)作为交联剂与接枝有硼酸的透明质酸反应。在近红外光照射下,M/P-PDA@IQ PHA 引起局部过热,触发肿瘤细胞和肿瘤相关抗原(TAA)的免疫原性细胞死亡和释放。随后,M/P-PDA@IQ PHA 通过 pH/ROS/GSH 触发的降解逐渐释放出 M/P-PDA@IQ NAs,可捕获并将这些 TAA 递送至淋巴结。最后,M/P-PDA@IQ NAs 促进树突状细胞的成熟和交叉呈递,以及细胞毒性 T 淋巴细胞的激活。总的来说,M/P-PDA@IQ PHA 可以作为一种新型的原位疫苗,刺激包括 TAA 释放和捕获、靶向淋巴结以及增强树突状细胞摄取和成熟以及 T 细胞激活等多个关键节点。这种级联免疫激活策略可以有效地引发抗肿瘤免疫反应。

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