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工程化 CaP-Pickering 乳液通过双重 DC 和 NK 激活增强 mRNA 癌症疫苗

英文原题:Engineering CaP-Pickering emulsion for enhanced mRNA cancer vaccines via dual DC and NK activations.

查看英文原题

Engineering CaP-Pickering emulsion for enhanced mRNA cancer vaccines via dual DC and NK activations.

PubMed 2024/08/03(内容时间) J Control Release Q1 · IF 12.4(JCR 2025)

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中文摘要

mRNA递送系统,如脂质纳米颗粒(LNP),在提高mRNA表达方面已取得显著进展,而免疫系统激活则存在阈值效应。维持抗原表达与树突状细胞(DC)激活之间的微妙平衡对于有效的免疫识别至关重要。在此,开发了一种由磷酸钙纳米颗粒稳定的水包油包水(w/o/w)Pickering乳液(CaP-PME),用于癌症疫苗中的mRNA递送。CaP-PME能有效地将mRNA转运至细胞质,通过破坏细胞内钙/钾离子平衡诱导促炎反应并激活DC。与LNP不同,CaP-PME表现出对DC的偏好性,增强其激活及向淋巴结的迁移。它引发干扰素-γ介导的CD8+ T细胞反应,并促进NK细胞增殖和激活,导致明显的NK细胞浸润和肿瘤微环境改善。所制备的w/o/w Pickering乳液在E.G7和B16-OVA肿瘤模型中表现出优越的抗肿瘤效果,作为癌症疫苗的增强型mRNA递送载体具有广阔前景。

展开英文摘要原文

mRNA delivery systems, such as lipid nanoparticle (LNP), have made remarkable strides in improving mRNA expression, whereas immune system activation operates on a threshold. Maintaining a delicate balance between antigen expression and dendritic cell (DC) activation is vital for effective immune recognition.

Here, a water-in-oil-in-water (w/o/w) Pickering emulsion stabilized with calcium phosphate nanoparticles (CaP-PME) is developed for mRNA delivery in cancer vaccination. CaP-PME efficiently transports mRNA into the cytoplasm, induces pro-inflammatory responses and activates DCs by disrupting intracellular calcium/potassium ions balance. Unlike LNP, CaP-PME demonstrates a preference for DCs, enhancing their activation and migration to lymph nodes.

It elicits interferon-γ-mediated CD8 + T cell responses and promotes NK cell proliferation and activation, leading to evident NK cells infiltration and ameliorated tumor microenvironment. The prepared w/o/w Pickering emulsion demonstrates superior anti-tumor effects in E. G7 and B16-OVA tumor models, offering promising prospects as an enhanced mRNA delivery vehicle for cancer vaccinations.

论文信息

作者
Wu S、Zhou Y、Asakawa N、Wen M、Sun Y、Ming Y、Song T、Chen W
第一作者单位
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100081, PR China; Division of Molecular Science, Graduate School of Science and Technology, Gunma University, 1-5-1, Tenjin-cho, Kiryu 376-8515, Japan.China
通讯作者单位
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100081, PR China; School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing 100049, PR China. Electronic address: yfxia@ipe.ac.cn.China
文献类型
非美国政府资助研究
期刊
Journal of controlled release : official journal of the Controlled Release Society2024 Sep
原文标识
PubMed 39059499 · DOI 10.1016/j.jconrel.2024.07.051