Minimalism in Radiation Synthesis of Biomedical Functional Nanogels

Abstract

A scalable, single-step, synthetic approach for the manufacture of biocompatible, functionalized micro-and nanogels is presented. In particular, poly(N-vinyl pyrrolidone)-grafted-(aminopropyl)methacrylamide microgels and nanogels were generated through e-beam irradiation of PVP aqueous solutions in the presence of a primary amino-group-carrying monomer. Particles with different hydrodynamic diameters and surface charge densities were obtained at the variance of the irradiation conditions. Chemical structure was investigated by different spectroscopic techniques. Fluorescent variants were generated through fluorescein isothiocyanate attachment to the primary amino groups grafted to PVP, to both quantify the available functional groups for bioconjugation and follow nanogels localization in cell cultures. Finally, a model protein, bovine serum albumin, was conjugated to the nanogels to demonstrate the attachment of biologically relevant molecules for targeting purposes in drug delivery. The described approach provides a novel strategy to fabricate biohybrid nanogels with a very promising potential in nanomedicine.

Oligonucleotides‐decorated‐poly(N‐vinyl pyrrolidone) nanogels for gene delivery

“…Electron beam irradiation was performed using the linear accelerator at the ICHTJ of Warsaw (Poland), Electronika 10/10. Irradiation was carried out at an average beam current of 0.45 mA, pulse length of 4.5 μs, and pulse repetition rate of 400 Hz . Samples were horizontally placed in a box filled with ice and conveyed under the beam via a transporting belt at a speed of 0.3 m/min.…”

“…An integrated dose of 40 kGy, within the sterilization dose range, was supplied with a single pass and at a dose‐rate of 13 Gy per pulse . After irradiation, samples were dialyzed (MWCO 100 kDa) against distilled water for 48 h to remove eventual unreacted monomer, oligomers, and low MW polymer and re‐equilibrate pH . The formulation had a pH of about 6.0 prior to irradiation, which turned to be 4.9 after irradiation and 5.8 after dialysis.…”

“…However, the development of therapeutic devices based on nanoparticles is still limited by the lack of synthetic strategies, which are simultaneously economically viable and able to grant a good degree of control over the device properties, especially when produced at a large scale. We have recently developed a single‐step synthetic platform to generate either carboxyl or primary amino groups bearing poly( N ‐vinyl pyrrolidone) (PVP) nanogels . The synthetic approach is based on high‐energy irradiation of semi‐dilute aqueous solutions of PVP in the presence of a functional group carrying acrylic monomer, namely acrylic acid.…”

“…Polymer crosslinking, monomer grafting and sterilization are simultaneously achieved. The manufacturing process does not require long purification procedures, as it does when recourse to surfactants is made, it can be easily scaled‐up at industrial level with high throughputs and it ensures high control over materials properties, like particles size, surface charge densities, and degree of functionalization . The produced nanogels, in virtue of the abundance of their reactive functional groups, can be decorated in mild reaction conditions with fluorescent probes and biomolecules .…”

“…The manufacturing process does not require long purification procedures, as it does when recourse to surfactants is made, it can be easily scaled‐up at industrial level with high throughputs and it ensures high control over materials properties, like particles size, surface charge densities, and degree of functionalization . The produced nanogels, in virtue of the abundance of their reactive functional groups, can be decorated in mild reaction conditions with fluorescent probes and biomolecules . Recently, several studies have demonstrated that nanogels can release active antisense oligonucleotides (ODN), which were shown to be able to produce some desired effects on gene expression in specific cell lines .…”