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免疫诱导碳点复合水凝胶作为光热衍生抗原库触发强大的抗肿瘤免疫反应。

Immunoinducible Carbon Dot-Incorporated Hydrogels as a Photothermal-Derived Antigen Depot to Trigger a Robust Antitumor Immune Response.

机构信息

Department of Central Laboratory, The Affiliated People's Hospital, Jiangsu University, Zhenjiang212002, P. R. China.

Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang212013, P. R. China.

出版信息

ACS Appl Mater Interfaces. 2023 Feb 15;15(6):7700-7712. doi: 10.1021/acsami.2c18371. Epub 2023 Jan 31.

DOI:10.1021/acsami.2c18371
PMID:36719405
Abstract

Immunogenic tumor cell death (ICD) induced by photothermal therapy (PTT) fails to elicit a robust antitumor immune response partially due to its inherent immunosuppressive microenvironment and poor antigen presentation. To address these issues, we developed an immunoinducible carbon dot-incorporated hydrogel (iCD@Gel) through a dynamic covalent Schiff base reaction using mannose-modified aluminum-doped carbon dots (M/A-CDs) as a cross-linking agent. The M/A-CDs possessed superior photothermal conversion efficiency and served as nanocarriers to load cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs) for inducing the maturation of dendritic cells (DCs) via mannose receptor-mediated targeting delivery. Upon intratumoral injection, the as-prepared iCD@Gel induced ICD, and damage-associated molecular patterns (DAMPs) were released via photothermal ablation under 808 nm NIR irradiation. Subsequently, the iCD@Gel synergized with the DAMPs to significantly promote the maturation and antigen cross-presentation ability of DCs. This work provides a promising strategy to develop carbon dot-based therapeutic hydrogels for photothermal therapy and immune activation.

摘要

免疫原性肿瘤细胞死亡(ICD)诱导的光热治疗(PTT)未能引发强烈的抗肿瘤免疫反应,部分原因是其固有的免疫抑制微环境和抗原呈递能力差。为了解决这些问题,我们通过使用甘露糖修饰的掺铝碳点(M/A-CDs)作为交联剂的动态共价席夫碱反应,开发了一种免疫诱导碳点水凝胶(iCD@Gel)。M/A-CDs 具有优异的光热转换效率,并作为纳米载体负载胞嘧啶-磷酸-鸟嘌呤寡脱氧核苷酸(CpG ODNs),通过甘露糖受体介导的靶向递送来诱导树突状细胞(DCs)的成熟。在肿瘤内注射后,所制备的 iCD@Gel 通过 808nm NIR 照射下的光热消融诱导 ICD,并释放损伤相关分子模式(DAMPs)。随后,iCD@Gel 与 DAMPs 协同作用,显著促进 DCs 的成熟和抗原交叉呈递能力。这项工作为基于碳点的治疗性水凝胶的光热治疗和免疫激活提供了一种很有前途的策略。

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