3.4.2. Hyaluronic Acid-Based Nanogels

These types of nanoparticles with physically or chemically crosslinked polymer chains possess pores that can be filled with macromolecules to target cancer cells, as initially demonstrated in vitro [181,182]. HA-based nanogels are used to improve the activity of delivering compounds, enhancing stability, and increasing the biological half-life of HA [178,183]. Indeed, several studies demonstrate the efficiency of HA-based nanogels as drug carriers [184,185]. Moreover, it is possible to link HA with coiled-coil peptide, creating a pH-sensitive nanogel for controled drug release to increase the anti-tumor effect on MCF-7 cells in vitro [186]. Furthermore, it was shown that HA nanogels, fabricated by the methacrylation strategy, are sensitive to enzyme action. The nanogels target cancer cells in a manner dependent on HA receptors expression and are deconstructed by the action of Hyals, releasing their drug load [185]. The introduction of cholesterol to crosslinked nanogels confers hydrophobicity to HA, increasing cell membranes' permeability to HAbased nanogels [187]. Another way to enhance the hydrophobic features of HA nanogels is to acetylate the HA backbone. Indeed, acetylation's degree affects Hela cells' drug loading efficiency and targeting in an in vitro experimental model [188].
