Radiation synthesis of nanogels as therapeutic agent vectors

Abstract

Nanogels (NGs) are physically or chemically crosslinked polymer networks and are promising candidates in the development of therapeutic agent vectors. In fact, thanks to their tunable size and properties, they offer unique advantages, including a large and flexible surface for multivalent bio-conjugation, an internal 3D aqueous environment for incorporation and protection of (bio)molecular drugs, stimuliresponsiveness to achieve temporal and/or site control of the release function and biocompatibility. In order to develop effective NGs-based biomedical devices an inexpensive, robust and versatile synthetic methodology is required. In this perspective, we have produced NGs with high yields and through-puts by pulsed electron-beam irradiation. In particular, using an industrial electron accelerator, carboxyl functionalized NGs from a dilute aqueous solutions of poly(N-vinyl pyrrolidone) (PVP), and acrylic acid as functional monomer have been produced. This process allows simultaneous polymer cross-linking and monomer grafting. Moreover, depending on the value of the total irradiation dose, also the sterilization of the irradiated material can be obtained. Since organic solvents, toxic initiators or catalysts and surfactants are not required, this procedure can be defined as an eco-friendly and clean one. Crosslinked nanoparticles with multi-armed surfaces, and size, crosslinking density, and surface electric charge density controlled, have been generated. Nanogels produced have been proven to be hemocompatible and not cytotoxic or genotoxic at the cellular level. NGs have been decorated with fluorescent probes, proteins and anti-MiR. Thanks to the use of fluorescent variants, it has been argued that NGs showed a good affinity for cells, as they rapidly and quantitatively bypass the cellular compartments, accumulating in specific cell portions for the first hours, and being completely released from the cells in the next 24 hours. Moreover, it has been proven that the proteins and anti-MiR, once conjugated, maintain their biological activity giving rise to targeting features toward specific cell types.