Bian Xiaochun, Zhou Liping, Luo Zhiwei, Liu Guotao, Hang Zhongci, Li Haohao, Li Fengyong, Wen Yongqiang
Beijing Key Laboratory for Bioengineering and Sensing Technology, Daxing Research Institute, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China.
Plastic Surgery Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.
ACS Nano. 2025 Feb 4;19(4):4039-4083. doi: 10.1021/acsnano.4c11858. Epub 2025 Jan 21.
Nucleic acid therapeutics represent a highly promising treatment approach in modern medicine, treating diseases at the genetic level. However, these therapeutics face numerous challenges in practical applications, particularly regarding their stability, effectiveness, cellular uptake efficiency, and limitations in delivering them specifically to target tissues. To overcome these obstacles, researchers have developed various innovative delivery systems, including viral vectors, lipid nanoparticles, polymer nanoparticles, inorganic nanoparticles, protein carriers, exosomes, antibody oligonucleotide conjugates, and DNA nanostructure-based delivery systems. These systems enhance the therapeutic efficacy of nucleic acid drugs by improving their stability, targeting specificity, and half-life in vivo. In this review, we systematically discuss different types of nucleic acid drugs, analyze the major barriers encountered in their delivery, and summarize the current research progress in emerging delivery systems. We also highlight the latest advancements in the application of these systems for treating genetic diseases, infectious diseases, cancer, brain diseases, and wound healing. This review aims to provide a comprehensive overview of nucleic acid drug delivery systems' current status and future directions by integrating the latest advancements in nanotechnology, biomaterials science, and gene editing technologies, emphasizing their transformative potential in precision medicine.
核酸疗法是现代医学中一种极具前景的治疗方法，可在基因水平上治疗疾病。然而，这些疗法在实际应用中面临诸多挑战，尤其是在稳定性、有效性、细胞摄取效率以及将其特异性递送至靶组织方面的局限性。为克服这些障碍，研究人员开发了各种创新的递送系统，包括病毒载体、脂质纳米颗粒、聚合物纳米颗粒、无机纳米颗粒、蛋白质载体、外泌体、抗体寡核苷酸缀合物以及基于DNA纳米结构的递送系统。这些系统通过提高核酸药物的稳定性、靶向特异性和体内半衰期来增强其治疗效果。在本综述中，我们系统地讨论了不同类型的核酸药物，分析了其递送过程中遇到的主要障碍，并总结了新兴递送系统的当前研究进展。我们还强调了这些系统在治疗遗传疾病、传染病、癌症、脑部疾病和伤口愈合方面应用的最新进展。本综述旨在通过整合纳米技术、生物材料科学和基因编辑技术的最新进展，全面概述核酸药物递送系统的现状和未来方向，强调其在精准医学中的变革潜力。
