PEG-PCL-DEX polymersome-protamine vector as an efficient gene delivery system via PEG-guided self-assembly

Aim: The nonviral carrier system based on the triblock copolymer PEG-PCL-DEX (PPD) and protamine was developed for nucleic acid delivery. Materials & methods: Self-assembly occurred in the PEG continuous phase to form 'dextran-interior' polymersomes. siRNA can be condensed by protamine and encapsulated into PPD polymersomes in order to form the PPD-protamine siRNA nanoparticles by thermodynamically preferential partition between the PEG continuous phase and the dextran cavity. Results: This system can package siRNA into PPD polymersomes to form 145.2 +/- 8.02-nm (+/- standard deviation) nanoparticles, and the zeta-potential can be reduced to approximately 0 mV. PPD-protamine siRNA nanoparticles achieved cellular uptake of siRNA in SMMC-7721 cells with negligible cytotoxicity, and the GL3 gene expression can be reduced to 61.73 +/- 6.25%. A biodistribution study of nanoparticles suggested that the PPD-protamine siRNA nanoparticles mainly accumulated in liver. Conclusion: All of these results suggest that PPD-protamine carriers may offer a promising gene delivery strategy for the treatment of liver-related disease.