{"title":"通过 DC 和 NK 双重激活工程 CaP-Pickering 乳化液来增强 mRNA 癌症疫苗。","authors":"","doi":"10.1016/j.jconrel.2024.07.051","DOIUrl":null,"url":null,"abstract":"<div><p>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<sup>+</sup> 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.</p></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":null,"pages":null},"PeriodicalIF":10.5000,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Engineering CaP-Pickering emulsion for enhanced mRNA cancer vaccines via dual DC and NK activations\",\"authors\":\"\",\"doi\":\"10.1016/j.jconrel.2024.07.051\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>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<sup>+</sup> 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.</p></div>\",\"PeriodicalId\":15450,\"journal\":{\"name\":\"Journal of Controlled Release\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":10.5000,\"publicationDate\":\"2024-08-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Controlled Release\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0168365924005066\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Controlled Release","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0168365924005066","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
摘要
mRNA递送系统,如脂质纳米颗粒(LNP),在改善mRNA表达方面取得了长足进步,而免疫系统的激活则有一个阈值。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。在此,我们开发了一种用磷酸钙纳米颗粒(CaP-PME)稳定的水包油包水(w/o/w)皮克林乳液,用于癌症疫苗中的 mRNA 递送。CaP-PME 能有效地将 mRNA 运送到细胞质中,诱导促炎反应,并通过破坏细胞内钙/钾离子平衡激活 DC。与 LNP 不同,CaP-PME 表现出对 DC 的偏好,能增强 DC 的活化和向淋巴结的迁移。它能引起干扰素-γ 介导的 CD8+ T 细胞反应,促进 NK 细胞的增殖和活化,从而导致明显的 NK 细胞浸润和肿瘤微环境的改善。制备的不含水分/重量的皮克林乳剂在 E.G7 和 B16-OVA 肿瘤模型中显示出卓越的抗肿瘤效果,有望成为癌症疫苗的增强型 mRNA 运送载体。
Engineering CaP-Pickering emulsion for enhanced mRNA cancer vaccines via dual DC and NK activations
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.
期刊介绍:
The Journal of Controlled Release (JCR) proudly serves as the Official Journal of the Controlled Release Society and the Japan Society of Drug Delivery System.
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