Kart Ulpan, Raimbekova Aigul, Yegorov Sergey, Hortelano Gonzalo
Department of Biology, School of Sciences and Humanities, Nazarbayev University, 53 Kabanbay Batyr Ave., Astana 010000, Kazakhstan.
Pharmaceutics. 2025 May 4;17(5):609. doi: 10.3390/pharmaceutics17050609.
The oral delivery of DNA/RNA nanoparticles represents a transformative approach in immunotherapy and vaccine development. These nanoparticles enable targeted immune modulation by delivering genetic material to specific cells in the gut-associated immune system, triggering both mucosal and systemic immune responses. Unlike parenteral administration, the oral route offers a unique immunological environment that supports both tolerance and activation, depending on the formulation design. This review explores the underlying mechanisms of immune modulation by DNA/RNA nanoparticles, their design and delivery strategies, and recent advances in their application. Emphasis is placed on strategies to overcome physiological barriers such as acidic pH, enzymatic degradation, mucus entrapment, and epithelial tight junctions. Special attention is given to the role of gut-associated lymphoid tissue in mediating immune responses and the therapeutic potential of these systems in oral vaccine platforms, food allergies, autoimmune diseases, and chronic inflammation. Despite challenges, recent advances in nanoparticle formulation support the translation of these technologies into clinical applications for both therapeutic immunomodulation and vaccination.
DNA/RNA纳米颗粒的口服给药是免疫疗法和疫苗开发中的一种变革性方法。这些纳米颗粒通过将遗传物质递送至肠道相关免疫系统中的特定细胞，实现靶向免疫调节，从而触发黏膜和全身免疫反应。与肠胃外给药不同，口服途径提供了一种独特的免疫环境，根据制剂设计，该环境既支持免疫耐受又支持免疫激活。本综述探讨了DNA/RNA纳米颗粒免疫调节的潜在机制、其设计和递送策略，以及它们在应用方面的最新进展。重点是克服生理屏障的策略，如酸性pH值、酶降解、黏液截留和上皮紧密连接。特别关注肠道相关淋巴组织在介导免疫反应中的作用，以及这些系统在口服疫苗平台、食物过敏、自身免疫性疾病和慢性炎症中的治疗潜力。尽管存在挑战，但纳米颗粒制剂的最新进展支持将这些技术转化为用于治疗性免疫调节和疫苗接种的临床应用。
