Chemoselective functionalization of nanogels for microglia treatment

The development of nanogels as nanoscale multifunctional polymer-based matrices for controlled drug and gene delivery purposes has been the subject of intense research during the last decades. Indeed, polymeric nanoparticles are capable to interact with cells to different extents, depending on their size, shape, surface properties and ligands tagged to the surface. Moreover, coating these devices using appropriate functionalization strategies can greatly improve or not their adhesion and uptake by cells. In this work, we proposed different coatings and then we studied their ability to improve or reduce microglia internalization. Nanogels (NGs) were composed by polyethylene glycol (PEG) and polyethyleneimine (PEI) conjugated with rhodamine through click chemistry reaction. Coatings were prepared using PEG monomethyl ether (mPEG), modifying its terminal hydroxyl groups with different linkers to evaluate the amount of mPEG layer chemically bond to the nanogel and its effect over microglia internalization. Nanogels were also investigated to identify which procedure is able to form networks with adequate dimensions and stability, according to the physicochemical parameters for the microglia applications in vitro. The biological experimental results showed that NGs were efficiently internalized by cells and the coating-microglia interactions allowed different cellular uptake. This outcome could be considered a promising perspective of nanogels use as carriers for drugs or genes delivery within microglia environment, improving their therapeutic effect through polymer surface modifications.