Smart nanoparticle-assisted nucleic acid delivery for targeted therapy and tissue repair

Tissue repair necessitates precise temporal regulation of cell proliferation, differentiation, and angiogenesis. Nucleic acid drugs exhibit significant therapeutic potential, but they encounter challenges such as low delivery efficiency, nuclease degradation, poor membrane penetration, and immunogenicity. Traditional gene delivery methods are hindered by instability, limited targeting capabilities, and uncontrolled release. In contrast, nanocarriers have emerged as ideal platforms due to their functionalization capabilities, biocompatibility, and ability to traverse physiological barriers. Among these, smart responsive delivery systems facilitate spatiotemporal drug release by harnessing microenvironmental signals from diseased tissues, thereby enhancing therapeutic accuracy and outcomes. This review summarizes recent advancements in nanocarrier-based nucleic acid delivery for tissue repair. It explores how carrier materials influence nucleic acid loading and cellular uptake, analyzes how targeted ligand modification regulates in vivo drug distribution, and discusses the construction strategies and efficacy of stimulus-responsive systems. Finally, it outlines potential applications of smart nucleic acid nanocarriers in tissue repair, aiming to establish a theoretical foundation for next-generation precision gene therapy platforms and facilitate the clinical translation of smart responsive delivery systems.