P-selectin targeting polysaccharide-based nanogels for miRNA delivery

Nanogels were prepared in aqueous media without the use of any organic solvent via a simple polyelectrolyte complexation method between aminated pullulan and fucoidan followed by covalent crosslinking with genipin. Homogeneously distributed genipin crosslinked nanogels (G-PECs) were obtained with a mean hydrodynamic diameter of similar to 155 nm and zeta potential of 0.86 +/- 4.35 mV. Their capacity to bind to human activated platelets was evaluated in vitro, as well as their cytocompatibility within human endothelial cells after 1 day of incubation up to 1000 mu g/mL of G-PECs (94.56 +/- 7.82% of viable cells). Additional hemolysis tests support the biocompatible character of the developed nanosystems (hemolysis rate of 2.09 +/- 0.06% for 1000 mu g/mL of G-PECs). Under acid conditions, the surface charge of G-PECs was tuned to around similar to 10 mV allowing miRNA incorporation via electrostatic interactions. G-PECs were able to promote miRNA delivery inside cells, as demonstrated by fluorescence microscopy images of labelled miRNA. With further studies to demonstrate the biological activity of delivered miRNA, these nanogels could be an interesting platform for miRNA-based therapeutics in atherothrombotic-related diseases thanks to the possibility to target over-expressed P-selectin.

Automated summary

This study successfully prepared biocompatible nanogels that exhibited excellent cytocompatibility and platelet binding ability in vitro, as well as improved miRNA delivery efficiency under acidic conditions.