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用于肿瘤免疫治疗的动态混合模块驱动 NK 细胞刺激与释放

英文原题:Dynamic Hybrid Module-Driven NK Cell Stimulation and Release for Tumor Immunotherapy.

查看英文原题

Dynamic Hybrid Module-Driven NK Cell Stimulation and Release for Tumor Immunotherapy.

PubMed 2024/04/19(内容时间) Nano Lett Q1 · IF 9.1(JCR 2025)

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中文摘要

自然杀伤(NK)细胞是过继肿瘤免疫治疗的强力候选,但治疗实体瘤的疗效仍不理想。本研究开发了一种由可注射水凝胶和羟基磷灰石(HAp)纳米带组成的混合模块,可控递送NK细胞以增强实体瘤治疗。表面功能化HAp纳米带修饰了针对NKG2D和4-1BB的激动性抗体,以及IL-2和IL-21细胞因子,可支持NK细胞存活并动态活化。因此,HAp修饰的壳聚糖(CS)热敏水凝胶不仅使NK细胞在体内滞留时间超过20天,还使NK细胞功能提高一倍以上。这种生物材料复合物的独特结构保护NK细胞免受肿瘤恶劣微环境影响并增强抗肿瘤效能。利用生物相容性水凝胶储库为NK细胞构建暂时性炎症生态位,可能成为预防可切除肿瘤癌症复发的转化途径。

展开英文摘要原文

Natural killer (NK) cells have become a powerful candidate for adoptive tumor immunotherapy, while their therapeutic efficacy in solid tumors remains unsatisfactory.

Here, we developed a hybrid module with an injectable hydrogel and hydroxyapatite (HAp) nanobelts for the controlled delivery of NK cells to enhance the therapy of solid tumors. Surface-functionalized HAp nanobelts modified with agonistic antibodies against NKG2D and 4-1BB and cytokines IL-2 and IL-21 support survival and dynamic activation.

Thus, the HAp-modified chitosan (CS) thermos-sensitive hydrogel not only improved the retention of NK cells for more than 20 days in vivo but also increased NK cell function by more than one-fold. The unique architecture of this biomaterial complex protects NK cells from the hostile tumor environment and improves antitumor efficacy. The generation of a transient inflammatory niche for NK cells through a biocompatible hydrogel reservoir may be a conversion pathway to prevent cancer recurrence of resectable tumors.

论文信息

作者
Jiao D、Hao M、Sun R、Ren X、Wei Y、Ding M、Yue X、Wu Z
第一作者单位
Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology, Cheeloo Medical College, Shandong University, Jinan 250000, China.China
通讯作者单位
State Key Laboratory of Crystal Materials, Shandong University, Jinan 250000, China.China
文献类型
非美国政府资助研究
期刊
Nano letters2024 May 8
原文标识
PubMed 38639407 · DOI 10.1021/acs.nanolett.4c00425