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In this work the influence of poly(N-vinyl pyrrolidone) (PVP) concentration in water on the organization and dynamics of the corresponding macro-/nanogel networks has been systematically investigated. Irradiation has been performed at the same irradiation dose (within the sterilization dose range) and dose rate. In the selected irradiation conditions, the transition between macroscopic gelation and micro-/nanogels formation is observed just below the critical overlap concentration (∼1 wt%), whereas the net prevalence of intra-molecular over inter-molecular crosslinking occurs at a lower polymer concentration (below 0.25 wt%). Dynamic–mechanical spectroscopy has been applied as a classical methodology to estimate the network mesh size for macrogels in their swollen state, while 13C NMR spin–lattice relaxation spectroscopy has been applied on both the macrogel and nanogel freeze dried residues to withdraw interesting information of the network spatial organization in the passage of scale from macro to nano.

Nanogels (NGs), or small particles formed by physically or chemically crosslinked polymer networks, represent a niche in the development of “smart” nanoparticles for drug delivery and diagnostics. They offer unique advantages over other systems, including a large and flexible surface for multivalent bio-conjugation; an internal 3D aqueous environment for incorporation and protection of (bio)molecular drugs; the possibility to entrap active metal or mineral cores for imaging or phototherapeutic purposes; stimuli-responsiveness to achieve temporal and/or site control of the release function and biocompatibility. The availability of inexpensive and robust preparation methodologies is at the basis of the development of effective nanogel-based theragnostic devices. The design rules for mass fabrication of nanoscale hydrogel particles with the recourse to industrial-type accelerators is here discussed.

Study of macromolecular structure and dynamics of networks formed by pulsed electron-beam irradiation of poly(N-vinyl pyrrolidone) (PVP) aqueous solutions, at relatively low energy per pulse and across different concentration regimes, provides the basis for the understanding of a new generation of functional nanostructures. Networks are the result of the follow-up reactions initiated by a continuous series of electron pulse-generated hydroxyl radicals, which may have a different fate at the variance of polymer concentration. Different spectroscopic techniques, FT-IR, 13C {1H} CP-MAS NMR and Raman, applied to characterize the formed networks, describe a profound modification of the chemical structure when network size is approaching the nanoscale. Static light scattering measurements provide further information on the average weight molecular weight modification of PVP when forming nanogel particles. From the simultaneous control of network size and modification of chemical functionality stems also an intrinsic fluorescence of these nanogels never observed before. Altogether the obtained radiation-sculptured nanogels exhibit interesting multifunctionality that, coupled with the already proven biocompatibility, can be exploited in the biomedical field.

Poly(N-vinylpyrrolidone)-grafted-acrylic acid biocompatible nanogels (NGs) were prepared using an exiting industrial-type electron accelerator and setups, starting from semi-dilute aqueous solutions of a commercial PVP and the acrylic acid monomer. As a result, NGs with tunable size and structure can be obtained quantitatively. Sterility was also imparted at the integrated dose absorbed. The chemical structure of the NGs produced was confirmed through Fourier Transformer Infrared Spectroscopy (FT-IR). The molecular and physico-chemical properties of NGs, such as the hydrodynamic dimensions and surface charge densities, for various polymer and monomer concentrations in the irradiated solutions, are discussed here.

(1) Background: A new family of nanosystems able to discern between normal and tumor cells and to release a therapeutic agent in controlled way were synthetized by e-beam irradiation. This technique permits to obtain biocompatible, sterile, carboxyl-functionalized polyvinylpyrrolidone (PVP-co-acrylic acid) nanogels (NGs); (2) Methods: Here, we performed a targeting strategy based on the recognition of over-expressed proteins on tumor cells, like the folate receptor. The selective targeting was demonstrated by co-culture studies and flow cytometry analysis, using folate conjugated NGs. Moreover, nanoparticles were conjugated to a chemotherapeutic drug or to a pro-apoptotic siRNA through a glutathione sensitive spacer, in order to obtain a controlled release mechanism, specific for cancer cells. The drug efficiency was tested on tumor and healthy cells by flow cytometric analysis, confocal and epifluorescence microscopy and cytotoxicity assay; the siRNA effect was investigated by RNAi experiment; (3) Results: The data obtained showed that the use of NGs permits a faster cargo release in cancer cells, in response to high cytosolic glutathione level, also improving their efficacy; (4) Conclusion: The possibility of releasing biological molecules in a controlled way and to recognize a specific tumor target allows overcoming the typical limits of the classic cancer therapy.

Aminopropyl methacrylamide chloride-graft-poly(N-vinyl pyrrolidone) nanogels (NGs) were designed to exploit the favorable properties of poly(N-vinyl pyrrolidone) (PVP), such as its high affinity to water and complexation ability of ions, molecules and macromolecules, with the availability of primary amino groups for bioconjugation reactions. A thorough structural characterization of the nanoscalar networks was performed via 1 H NMR and solid state 13 C NMR spectroscopies, while solid state NMR relaxation time measurements completed the NGs description in terms of polymer network density. Information on the hydrodynamic size and surface charge densities were sought via dynamic light scattering (DLS) and ζ-potential measurements. These measurements, carried out both in water and in buffer and at the variance of pH, temperature and time, support the excellent colloidal stability of the amino-graft PVP nanogels and their redispersability from the dry physical form. The total absence of in vitro toxicity and immunogenicity was ascertained first, and then cell localization studies in cell cultures of fluorescent variants were performed. Furthermore, the possibility of decorating the nanogels with bovine serum albumin (BSA) to obtain a stable bio-hybrid colloidal nanoconstruct was established. All the gathered evidences qualify these materials as potential candidates to be used as nanocarriers for intra-cellular delivery of protein and other biomolecular drugs.