Developing simple, safe and efficient non-viral delivery systems remains a major challenge in the field of bioengineering. Nanoparticles have promising gene delivery capabilities and low toxicity; however, for a long time, challenges related to effective plasmid encapsulation and delivery have existed. This paper reports a novel protein-based nanoparticle platform, fabricated by electrophoretic jetting, with effective plasmid encapsulation and release capabilities. The protein serum albumin serves as the structural component of the nanoparticles, encapsulating the plasmid. To avoid chemical cross-linking, the protein-based nanoparticles are surface-enclosed through an interface complex with multivalent cationic polymers. Surface-coated protein nanoparticles (scPNPs) exhibit excellent stability at physiological pH values and have an extremely high payload ratio, reaching 10% to 40% wt/wt, equivalent to 28–99 plasmids per scPNP. The uptake efficiency of scPNPs exceeds 95%, and they participate in the giant cell proliferation and gridin protein-mediated endocytosis pathway. When optimizing non-viral gene therapy, the payload or nanoparticle dose can be adjusted. For scPNPs, increasing the nanoparticle dose is more effective than increasing the payload, resulting in a 1.6-fold increase in transfection rate at the same plasmid quantity. To demonstrate its translational potential, scPNPs were used to effectively encapsulate messenger RNA (mRNA) and transfect primary human T cells while maintaining high cell survival rates. This work not only advances the basic understanding of optimizing nanoparticle gene delivery design choices but also demonstrates the potential of scPNPs in cell therapy.
This research was published in Advanced Materials under the title "Surface-Capped Protein Nanoparticles for Nonviral Gene Delivery". References:
DOI: 10.1002/adma.202521796