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一种抗体样聚合物纳米颗粒去除肿瘤内半乳糖凝集素-1 以增强癌症免疫治疗中的抗肿瘤 T 细胞反应。

An Antibody-like Polymeric Nanoparticle Removes Intratumoral Galectin-1 to Enhance Antitumor T-Cell Responses in Cancer Immunotherapy.

机构信息

Key Laboratory of Functional Polymer Materials of Ministry of Education, College of Chemistry, Nankai University, Tianjin 300071, China.

State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China.

出版信息

ACS Appl Mater Interfaces. 2021 May 19;13(19):22159-22168. doi: 10.1021/acsami.1c02116. Epub 2021 May 6.

Abstract

Antibodies have shown potential to deplete immunosuppressive factors in tumor tissues. However, intrinsic drawbacks, including time-consuming processes in preparation, high cost, and short half-life time, greatly restrict their applications. In this work, we report an antibody-like polymeric nanoparticle (APN) that is capable of specifically capturing and removing galectin-1 in tumor tissues, thereby enhancing the antitumor T-cell responses. The APN is composed of an albumin-polymer hybrid nanoparticle (core) and an acid-responsive PEG shell. The core of the APN contains multiple recognition units and Tuftsin peptides to capture target factors and activate macrophage-mediated phagocytosis, respectively. By employing galactose as recognition units, the APN facilitated the phagocytosis of galectin-1 in tumor tissues, thereby improving the antitumor responses of tumor-infiltrating T cells. Since the recognition units in the APN can be further replaced to capture and remove other peptides/proteins, the APN provides a feasible approach for the development of synthetic nanoformulations to regulate biological systems and treat diseases.

摘要

抗体已显示出在肿瘤组织中耗尽免疫抑制因子的潜力。然而,内在的缺陷,包括制备过程耗时、成本高和半衰期短,极大地限制了它们的应用。在这项工作中,我们报告了一种类似抗体的聚合物纳米颗粒(APN),它能够特异性地捕获和去除肿瘤组织中的半乳糖凝集素-1,从而增强抗肿瘤 T 细胞反应。APN 由白蛋白-聚合物杂化纳米颗粒(核心)和酸响应性 PEG 壳组成。APN 的核心包含多个识别单元和 Tuftsin 肽,分别用于捕获靶因子和激活巨噬细胞介导的吞噬作用。通过使用半乳糖作为识别单元,APN 促进了肿瘤组织中半乳糖凝集素-1的吞噬作用,从而提高了肿瘤浸润 T 细胞的抗肿瘤反应。由于 APN 中的识别单元可以进一步被替换以捕获和去除其他肽/蛋白质,因此 APN 为开发用于调节生物系统和治疗疾病的合成纳米制剂提供了一种可行的方法。

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