Stimuli-responsive polysaccharide nanogels for the targeted treatment of cancer

Self-assembled nanogels, nanometer-sized hydrogels obtained by physical self-assembly of interactive hydrophilic polymers, have attracted growing interest for drug delivery as these systems combine the advantages of hydrogels... [ view full abstract ]

Self-assembled nanogels, nanometer-sized hydrogels obtained by physical self-assembly of interactive hydrophilic polymers, have attracted growing interest for drug delivery as these systems combine the advantages of hydrogels with nanoscale formulations.[1-3] Such systems can be designed to facilitate the encapsulation of diverse classes of bioactive compounds as well as to release them in response to stimuli. Moreover, their hydrophilic shell can be exploited to control their biological fate and targeting ability. In this regard, self-assembled nanogels made of polysaccharides hold promise as a versatile nanocarrier, due to the presence of various functional groups on shell-forming polysaccharides in addition to their unique physicochemical properties, including biocompatibility and biodegradability. Among them, hyaluronic acid (HA) has been widely explored to fabricate nanogels as anti-cancer drug carriers due to the interesting biological properties of this natural polysaccharide.[4,5]  Indeed, HA is a glycosaminoglycan specifically recognized by the CD44 receptor that is overexpressed by several cancer cells. In this respect, we recently focused our efforts on engineering HA-copolymer conjugates to produce nanogels exhibiting a favorable balance between long circulation and moderate stability to release their payload at the targeted location (i.e. tumor site). We will show how precise control over functionalization of HA, as well as other glycosaminoglycans, and copolymer architecture can induce original physico-chemical and biological properties of polysaccharide-based nanogels. We will also present a new family of self-assembled nanogels obtained by boronate ester bond formation between biocompatible polysaccharides. The original feature of these gels nanoparticles, in particular their sensitivity to acidic pH, can be exploited for intracellular triggered disassembly and drug release in cancer cells.