Bioinspired pyrimidine-containing cationic polymers as effective nanocarriers for DNA and protein delivery

Cationic polymers have shown great potential in the delivery of nucleic acids and proteins. In this study, a series of pyrimidine-based cationic polymers were synthesized via the Michael addition reaction from pyrimidine-based linkages and low molecular weight polyethyleneimine (PEI). The structure–activity relationship (SAR) of these materials in DNA and protein delivery was investigated. These materials could condense both DNA and protein into nanoparticles with proper sizes and zeta-potentials. In vitro experiments indicated that such polymers were efficient in transporting DNA and proteins into cells. Furthermore, the bioactivity of the genes and proteins encapsulated in these polymers were maintained during the delivery processes. Among the polymers, U-PEI600 synthesized from a uracil-containing linker and PEI 600 Da mediated comparable gene expression to PEI 25 kDa. Moreover, the activities of β-galactosidase delivered by U-PEI600 were well maintained after entering the cells. Evaluation using an immune response assay showed that the U-PEI600/OVA polyplex could stimulate greater production of immune factors with low cytotoxicity. Our study provides a strategy for the construction of cationic polymeric gene and cytosolic protein vectors with high efficiency and low toxicity.