Nanogels designed for cell-free nucleic acid sequestration

Abstract

Chronic wounds exhibit over-expression of cell-free deoxyribonucleic acid (cfDNA), leading to a prolonged inflammation and non-healing wounds. Scavenging excessive cfDNA molecules is a promising strategy for chronic wound treatment. Nanoscopic particles act as efficient cfDNA scavengers due to their large surface area, however their efficiency in cfDNA uptake was limited by adsorption solely on the nanoparticle surface. In contrast, nanogels may provide multiple cfDNA binding sites in the nanoparticle interior, however their use for cfDNA scavenging is yet to be explored. Herein, we report cationic nanogels derived from a copolymer of chitosan and poly{2-[(acryloyloxy)ethyl]trimethylammonium chloride} end-grafted to the chitosan backbone as side chains. The nanogels retain their positive charge at the pH and ionic strength of chronic wound exudate, enabling electrostatically driven cfDNA scavenging. The network structure of the nanogels leads to the cfDNA sequestration in the nanogel interior, in addition to surface attachment. A key factor in cfDNA sequestration is the ratio of the pore size of the nanogel-to-cfDNA molecular dimensions. The enhanced cfDNA scavenging efficiency, along with biocompatibility of the nanogels, makes them a promising component of dressings for chronic wound treatment.