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海藻酸钠-明胶水凝胶微球在低氧条件下保护 NK 细胞的增殖和细胞毒性。

Alginate-gelatine hydrogel microspheres protect NK cell proliferation and cytotoxicity under hypoxic conditions.

机构信息

Department of Biological Engineering, Inha University, Incheon, Korea.

Industry-Academia Interactive R&E Center for Bioprocess Innovation, Inha University, Incheon, Korea.

出版信息

J Microencapsul. 2024 Aug;41(5):375-389. doi: 10.1080/02652048.2024.2362170. Epub 2024 Jun 30.

DOI:10.1080/02652048.2024.2362170
PMID:38945166
Abstract

AIMS

This study aimed to encapsulate natural killer (NK) cells in a hydrogel to sustain their function within the hypoxic tumour microenvironments.

METHODS

An alginate-gelatine hydrogel was generated via electrospray technology. Hydrogel biocompatibility was assessed through cell counting kit-8 and Live/Dead assays to ascertain cell. Moreover, we analysed lactate dehydrogenase assays to evaluate the cytotoxicity against tumours and utilised RT-qPCR to analyse cytokine gene level.

RESULTS

Alginate and gelatine formed hydrogels with diameters ranging from 489.2 ± 23.0 μm, and the encapsulation efficiency was 34.07 ± 1.76%. Encapsulated NK cells exhibited robust proliferation and tumour-killing capabilities under normoxia and hypoxia. Furthermore, encapsulation provided a protective shield against cell viability under hypoxia. Importantly, tumour-killing cytotoxicity through cytokines upregulation such as granzyme B and interferon-gamma was preserved under hypoxia.

CONCLUSION

The encapsulation of NK cells not only safeguards their viability but also reinforces anticancer capacity, countering the inhibition of activation induced by hypoxia.

摘要

目的

本研究旨在将自然杀伤 (NK) 细胞包封在水凝胶中,以维持其在缺氧肿瘤微环境中的功能。

方法

通过电喷雾技术生成藻酸盐-明胶水凝胶。通过细胞计数试剂盒-8 和 Live/Dead 测定法评估水凝胶的生物相容性,以确定细胞活力。此外,我们分析乳酸脱氢酶测定法以评估对肿瘤的细胞毒性,并利用 RT-qPCR 分析细胞因子基因水平。

结果

藻酸盐和明胶形成的水凝胶直径范围为 489.2±23.0μm,包封效率为 34.07±1.76%。在常氧和缺氧条件下,包封的 NK 细胞表现出强大的增殖和杀伤肿瘤能力。此外,包封在缺氧条件下为细胞活力提供了保护屏障。重要的是,通过上调细胞因子(如颗粒酶 B 和干扰素-γ),在缺氧条件下保持了肿瘤杀伤的细胞毒性。

结论

NK 细胞的包封不仅保护了它们的活力,还增强了抗癌能力,对抗由缺氧引起的激活抑制。

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