Nucleic acid vaccines have emerged as revolutionary platforms for infectious disease prevention and cancer immunotherapy. However, their clinical translation is significantly hindered by sequential biological barriers, necessitating highly efficient delivery systems. Biomedical polymers, owing to their tunable physicochemical properties, versatile structural engineering, and robust biocompatibility, have become a cornerstone in the development of nucleic acid nanocarriers. This review provides a comprehensive overview of polymeric delivery vehicles for nucleic acid vaccines, with a specific focus on rational design strategies tailored to overcome complex physiological barriers. We systematically dissect how functional polymer engineering-including interfacial shielding, targeted ligand modification, membrane perturbation, and stimuli-responsive disassembly-facilitates systemic circulation, antigen-presenting cell uptake, endosomal escape, and intracellular cargo release. Furthermore, we critically examine the persistent bottlenecks in current delivery platforms, such as the restricted uptake in primary immune cells and the fundamental inefficiencies of endosomal escape, while outlining future perspectives for the development of next-generation, clinically translatable polymeric nucleic acid vaccines.
Pijun Su, Huilin Yuan, Kangxin Zhang et al.· ACS Applied Materials and In...· 0 citations
RNA therapeutics have emerged as versatile platforms for gene modulation and protein expression in vaccination, oncology, genetic disorders, and inflammatory diseases. However, their broader clinical application remains limited by inefficient delivery, insufficient tissue specificity, inadequate intracellular bioavailability, and long-term safety concerns. This review examines non-viral and non-lipid RNA nanocarriers from mechanistic and translational perspectives. We outline the cargo-specific delivery requirements of various RNA modalities and analyze polymeric nanoparticles, inorganic nanomaterials, peptide- and protein-based carriers, and virus-like particles as distinct strategies to overcome extracellular, tissue-level, cellular, and intracellular barriers. Cross-platform trade-offs are evaluated based on RNA association and release, cargo compatibility, administration route, biodegradability, immune interactions, and manufacturability. We further discuss how carrier architecture influences biodistribution, intracellular RNA activity, and therapeutic efficacy across major disease areas. Clinically validated lipid nanoparticle (LNP) formulations serve as translational benchmarks, while non-lipid systems are evaluated based on productive delivery, release efficiency, repeat-dose compatibility, long-term material fate, scalability, and regulatory feasibility. By integrating cargo requirements, barrier resolution, intracellular trafficking, and translational benchmarking, this review highlights non-viral and non-lipid nanocarriers as complementary platforms for context-specific RNA therapy.
Mingxia Jiang, Qiannan Cao, Huapan Fang et al.· Journal of Controlled Releas...· 0 citations