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.
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.
J Control Release. 2024 Sep;373:837-852. doi: 10.1016/j.jconrel.2024.07.051. Epub 2024 Aug 3.
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.
mRNA 递送系统，如脂质纳米颗粒（LNP），在提高 mRNA 表达方面取得了显著进展，而免疫系统的激活则是基于一个阈值。在抗原表达和树突状细胞（DC）激活之间保持微妙的平衡对于有效的免疫识别至关重要。在这里，开发了一种由磷酸钙纳米颗粒（CaP-PME）稳定的油包水包油（w/o/w）Pickering 乳液用于癌症疫苗接种中的 mRNA 递送。CaP-PME 有效地将 mRNA 转运到细胞质中，通过破坏细胞内钙离子/钾离子平衡来诱导促炎反应并激活 DC。与 LNP 不同，CaP-PME 优先作用于 DC，增强其激活和向淋巴结的迁移。它引发干扰素-γ介导的 CD8 T 细胞反应，并促进 NK 细胞的增殖和激活，导致明显的 NK 细胞浸润和改善肿瘤微环境。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异的抗肿瘤效果，为癌症疫苗接种提供了一种有前景的增强型 mRNA 递送载体。
