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基于细菌酸盐的双功能mRNA纳米配方,用于有效的结肠癌免疫疗法

Xiaohua Chen¹, Jieping Wu¹, Bailing Zhou¹

¹State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, People's Republic of China.

ACS applied materials & interfaces

|October 14, 2024

概括

这项研究引入了一种新的双功能mRNA输送系统,使用Lactobacillus reuteri lysate来增强癌症免疫疗法. 该系统在提供IL-23AmRNA方面表现出高效率,并在临床前模型中显著抑制瘤生长.

科学领域:

生物医学工程生物医学工程
免疫学免疫学免疫学
纳米技术纳米技术

背景情况:

基于mRNA的非病毒基因疗法对癌症治疗有希望,但在治疗效率和治疗能力方面面临挑战.
免疫原疗法,利用免疫系统对抗癌症,是一个不断发展的策略.
肠道细菌Lactobacillus reuteri具有免疫调节特性,有利于减少炎症.

研究的目的:

开发一种双功能mRNA输送系统,用于增强癌症免疫治疗.
为了研究Lactobacillus reuteri lysate作为mRNA传递系统的组成部分的潜力.
在临床前癌症模型中评估开发系统的有效性.

主要方法:

准备一个双功能mRNA传递系统,DMP-Lac,代码传递Lactobacillus reuteri lysate和IL-23A mRNA.
在体内评估mRNA传递效率和免疫系统激活.
在CT26腹部和肺转移模型中评估治疗效果.
利用蛋白质芯片技术来阐明它的作用机制.

主要成果:

DMP-Lac/IL-23A系统实现了75.56%±0.85%的高mRNA传递效率.
该系统有效地促进了体内免疫系统的成熟和激活.
在转移模型中观察到显著的治疗效果,DMP-Lac/IL-23A组的瘤抑制率为97.92%.
乳杆菌reuteri lysate作为一个免疫辅助剂,调节免疫细胞,而IL-23mRNA影响下游因素.

结论:

开发的双功能mRNA配方,DMP-Lac/IL-23A,作为一种瘤特定的纳米药物.
该系统显示出强大的抗癌免疫治疗效果.
它通过将向mRNA输送与免疫刺激相结合,为结肠癌免疫基因疗法提供了一种先进的策略.

关键词:

它们的IL-23A.乳杆菌reuteri溶解酸的乳杆菌.免疫原疗法是一种免疫疗法.肠道菌群是指肠道上的植物.提供mRNA的交付.

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