Abstract Nucleic acid vaccines play a pivotal role in the development of advanced vaccine technologies for combating infectious diseases. However, the clinical translation of employed vaccine often encounters challenges, such as limited transfection efficacy and suboptimal biocompatibility. Therefore, it is urgent to develop efficient and safe nucleic acid delivery system. This study proposes a novel strategy based on polyglutamic acid (PGA) coated nanoparticles as potential vaccines for nucleic acid delivery. By harnessing poly(beta-amino ester) (PBAE) and nucleic acids to fabricate the self-assembly nanoparticles, the PGA-modified nanoparticles (PNPs) were subsequently manufactured following by the addition of PGA. The synthesis, characterization, and evaluation of the performance of PNPs were carried out. The results demonstrated that, PNPs exhibit favorable biophysical characteristics including well-controlled particle size, low zeta potential, and exceptional serum stability. Furthermore, the PGA modification of PNPs augments the lysosomal escape capability mediated by the polymer PBAE, thereby synergistically enhancing nucleic acid transfection efficacy. In summary, the utilization of PGA-modified nanoparticles holds great potential for achieving heighted nucleic acid transfection efficiency, thereby providing insight into the formulations design for nucleic acid vaccine and ultimately advancing the field of infectious disease prevention.
Received: 26 February 2024
Published: 25 February 2024