Dual-Functionalized Calcium Nanocomplexes for Transfection of Cancerous and Stem Cells: Low Molecular Weight Polycation-mediated Colloidal Stability and ATP-mediated Endosomal Release

Abstract To overcome colloidal instability of calcium phosphate nanoparticles in gene delivery, colloidally stable and endosomolytic Ca 2+ -based pDNA nanocomplexes (NCs) were designed by a surface coating of biocompatible polycations (PCs; low molecular weight branched polyethyleneimine [bPEI], protamine sulfate and e-polylysine) and the addition of natural and endosomolytic ATP, respectively. Without remarkable cytotoxicity and colloidal instability, Ca 2+ /ATP-pDNA/bPEI 1.8 kDa NCs having [bPEI 1.8 kDa ] = 3.6 μg showed 5.8-fold and 4.4-fold higher transfection efficiencies than bPEI 25 kDa /pDNA NCs in HepG2 cells and dental pulp stem cells, respectively. In conclusion, pH-sensitive endosomolytic ATP and Ca 2+ -based gene complexes could be potentials as effective and safe gene delivery vectors in various cells.