核酸疫苗已成为现代传染病疫苗中的研究热点，然而，核酸疫苗的临床转化仍然面临着转染效率低下和生物相容性不佳等瓶颈，迫切需要研发安全、高效的核酸递送载体。本研究提出一种新的核酸递送策略，在聚(β-氨基酯)[poly(β-amino ester)，PBAE]和核酸自组装形成PBAE纳米颗粒(PBAE nanoparticles，PBAE-NPs)的基础上，进一步采用聚谷氨酸[poly(glutamic acid)，PGA]进行修饰，形成PGA修饰的PBAE纳米颗粒(PGA modified PBAE nanoparticles，PPs)。本文将通过结构表征和生物学评价探究PPs作为核酸递送载体的性能。体外表征结果显示，PPs具有粒径小、Zeta电位低和血清稳定性强等良好的生物学特性。细胞溶酶体逃逸实验结果表明，PGA修饰能够提高PPs的溶酶体逃逸能力。流式细胞术结果表明，相较于PBAE-NPs，PPs显著增强了核酸转染效率。此外，CCK-8实验结果显示，PPs具有良好的生物安全性。综上所述，PPs具有安全性好、核酸转染效率高等特点，是一种具有开发前景的核酸递送载体，为今后核酸疫苗载体的设计提供了新的思路。

Nucleic acid vaccines play a pivotal role in the development of advancing vaccine technologies against infectious diseases. Despite their potential, the clinical application of nucleic acid vaccines still faces hurdles including limited transfection efficacy and suboptimal biocompatibility. Addressing these challenges, this study introduced a novel strategy utilizing the self-assembly of poly(β-amino ester) (PBAE) with nucleic acids to form PBAE nanoparticles (PBAE-NPs). PBAE-NPs were further modified with poly(glutamic acid) (PGA) to produce PGA modified PBAE nanoparticles (PPs) as potential nucleic acid delivery carriers. Comprehensive synthesis, structural characterization, and biological evaluation of PPs were performed. The characterization results demonstrated that PPs exhibited favorable biological characteristics, such as well-controlled particle size, low zeta potential, and exceptional serum stability. The lysosomal escape experiment results showed that PPs had good lysosomal escape ability endowed with PGA. Flow cytometry results indicated that PPs exhibited significantly enhanced nucleic acid transfection efficiency compared to PBAE-NPs. The CCK-8 results showed that PPs had good biocompatibility. Collectively, these results suggest that PPs could significantly improve nucleic acid transfection efficiency, thereby providing insight into the formulations design for nucleic acid vaccines.