Mussel-inspired polydopamine-polyethylenimine conjugated nanoparticles as efficient gene delivery vectors for mammalian cells

Abstract

Efficient delivery of DNA to cells is the primary concern to address the objective of gene therapy. Many attempts have been made to develop polymeric carriers for gene delivery. To have an efficient carrier, it is vital to understand the properties of the vector for better stability, transfection efficiency and minimal toxicity. Branched polyethylenimine (bPEI) has been considered as the ‘gold standard’ for gene delivery but suffers a major drawback of exhibiting high cytotoxicity. Here, we have attempted to develop a mussel-derived polymer, polydopamine (PDA), conjugated polyethylenimine nanoparticles in such a way that the toxic nature of bPEI is suppressed by the conversion of free primary amine groups to secondary and tertiary amines. Keeping the amount of PDA fixed, varying amounts of bPEIs of different molecular weights (25, 10 and 1.8kDa) were conjugated via Michael addition and/or Schiff base. A trend in hydrodynamic size of the conjugated nanoparticles was observed in the range from 160 to 300nm and zeta potential from +12–30mV in the projected three series, viz., (i) PDA1-25bPEI0.5, PDA1-25bPEI1, PDA1-25bPEI2; (ii) PDA1-10bPEI0.5, PDA1-10bPEI1, PDA1-10bPEI2; and (iii) PDA1-1.8bPEI0.5, PDA1-1.8bPEI1, PDA1-1.8bPEI2. A visible trend in the DNA condensation ability and buffering capacity was also noticed. Further, cell cytotoxicity assays revealed that pDNA complexes of PDA-bPEI nanoparticles were non-toxic to mammalian cells and these complexes exhibited several folds higher transfection efficiency than the complexes of native bPEIs as demonstrated by fluorescence measurements and flow cytometry. Altogether, the results advocate the promising potential of these conjugated nanoparticles for future in vivo applications.