We report the formulation of novel composite nanoparticles that combine the high transfection efficiency of cationic peptide-DNA nanoparticles with the biocompatibility and prolonged delivery of polylactic acid-polyethylene glycol (PLA-PEG). The cationic cell-penetrating peptide RALA was used to condense DNA into nanoparticles that were encapsulated within a range of PLA-PEG copolymers. The composite nanoparticles produced exhibited excellent physicochemical properties including size <200 nm and encapsulation efficiency >80%. Images of the composite nanoparticles obtained with a new transmission electron microscopy staining method revealed the peptide-DNA nanoparticles within the PLA-PEG matrix. Varying the copolymers modulated the DNA release rate >6 weeks in vitro. The best formulation was selected and was able to transfect cells while maintaining viability. The effect of transferrin-appended composite nanoparticles was also studied. Thus, we have demonstrated the manufacture of composite nanoparticles for the controlled delivery of DNA.
Int J Nanomedicine
7183 - 7196
DNA, PLA-PEG, cationic peptide, composite nanoparticles, gene delivery, transfection, Cations, Cell Line, Tumor, Cell Survival, Cell-Penetrating Peptides, DNA, Electrophoretic Mobility Shift Assay, Gene Transfer Techniques, Humans, Nanoparticles, Particle Size, Peptides, Polyethylene Glycols, Temperature, Transfection