摘要
在基因治疗中引入免疫系统激活组分成是一种很有前景的癌症免疫治疗策略。然而，目前仍然缺乏能够在具有免疫激活能力的同时保持高效基因递送效率的理想非病毒基因传递系统。作为肠道益生菌的一员，罗伊氏乳杆菌与癌症进展具有潜在的相关性，其独特的抗原也具有潜在的免疫调节活性。我们设计了一种新的非病毒siRNA递送系统DMP-Lac，通过使用基因递送载体DMP封装罗伊氏乳杆菌裂解物，增强抗癌免疫刺激特性。我们制备的DMP-Lac纳米颗粒的siRNA递送效率高达97.62%。同时，DMP-Lac在体外和体内均能促进DC和T细胞等免疫细胞的成熟和活化。吸附靶向免疫检查点CD47的siRNA后，DMP-Lac/siCD47复合物可以安全地抑制多种结肠癌模型的生长。总之，我们的研究开发了一种基于肠道益生菌裂解物的新型基因递送系统，为癌症免疫治疗提供了一种潜在的策略。
关键词： siRNA；肠道益生菌；免疫治疗；CD47
Abstract
The introduction of immune system activation in gene therapy is a promising strategy for cancer. However, there is still a lack of ideal non-viral gene delivery system that can maintain high gene delivery efficiency while maintaining immune activation ability. As a member of intestinal probiotics, Lactobacillus reuteri has potential relevance to cancer progression, and its unique antigens also have potential immunomodulatory activity. We designed a novel non-viral siRNA delivery system, DMP-Lac, to enhance anti-cancer immunostimulatory properties by encapsulating Lactobacillus royi lysate using gene delivery vector DMP. The siRNA delivery efficiency of DMP-Lac nanoparticles prepared is as high as 97.62%. At the same time, DMP-Lac can promote the maturation and activation of immune cells such as DC and T cells in vitro and in vivo. After adsorption of siRNA targeting immune checkpoint CD47, DMP-Lac/siCD47 complex can safely inhibit the growth of multiple colon cancer models. In conclusion, our study developed a novel gene delivery system based on gut probiotic lysate, providing a potential strategy for cancer immunotherapy.
Key words： siRNA; intestinal probiotics; immunotherapy; CD47
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