Surface hydrolysis-mediated PEGylation of poly(N-isopropyl acrylamide) based nanogels

Abstract

In this work, poly(N-isopropyl acrylamide-co-acrylamide) [P(NIPAAm-co-AAm)] nanogels were modified by hydrolysis above the lower critical solution temperature (LCST) to localize carboxylic acid functional groups at the surface (surface hydrolysis). PNIPAAm copolymerized with 15% and 20% nominal AAm in the feed were prepared and compared to equivalent hydrogels with acrylic acid. The effect and extent of surface hydrolysis was confirmed by potentiometric titration and zeta potential. These surface modified nanogels were then modified with primary amine functionalized PEG chains. Surface hydrolysis-mediated PEGylation had little effect on the swelling response of the nanogels, while also preventing adsorption of model proteins in physiological relevant conditions. While both 15% and 20% AAm gels both decreased protein adsorption, only the 20% AAm gels resulted in fully preventing protein adsorption. The results presented here point to surface hydrolysis as a new route to passivate nanogels for use in vivo.

Supramolecular Hydrogels: Design Strategies and Contemporary Biomedical Applications

“…Hard nanoparticles are synthesised from materials including gold, silica, carbon nanotubes and polymeric nanoparticles (with a high glass transition temperature), whereas soft nanoparticles are primarily based on liposomes, polymeric micelles, dendrimers and nanogels. [81][82][83] While they generally present a highly ordered structure, intrinsic functionalities (such as localised surface plasmon resonance) and fair ex and in vivo stability -which are all desirable from a materials design perspective -hard inorganic nanoparticles can promote adverse inflammatory responses and become toxic when they accumulate in a region of the tissue. [84] As a result, soft nanoparticles which present the inert, insulating properties of organic structures, are more suited to applications requiring biocompatibility.…”

“…Soft nanoparticles are those with a compressive modulus similar to that of a natural hydrogel, whilst hard nanoparticles are much more resistant to compression. Hard nanoparticles are synthesised from materials including gold, silica, carbon nanotubes and polymeric nanoparticles (with a high glass transition temperature), whereas soft nanoparticles are primarily based on liposomes, polymeric micelles, dendrimers and nanogels [81–83] . While they generally present a highly ordered structure, intrinsic functionalities (such as localised surface plasmon resonance) and fair ex and in vivo stability – which are all desirable from a materials design perspective – hard inorganic nanoparticles can promote adverse inflammatory responses and become toxic when they accumulate in a region of the tissue [84] .…”

Thermoresponsive Nanogels Based on Different Polymeric Moieties for Biomedical Applications

“…Hydrophobic units like methyl and ethyl groups can regulate the polarity and temperature-responsiveness of the polymer within a physiological temperature range [ 143 ]. The composition of the monomers, molecular weight, concentration, and ionic strength of the solution considerably affect the LCST of PEG-based copolymers [ 144 ]. Xia Dong et al synthesized a thermosensitive fluorescent nanogel using the four-arm PEG–PCL for bio-imaging applications.…”

Soft‐Nanoparticle Functionalization of Natural Hydrogels for Tissue Engineering Applications

“…Hard nanoparticles can be fabricated from materials such as silica, gold, quantum dots, carbon nanotubes, graphene sheets, and polymeric nanoparticles. Whereas soft nanoparticles with mechanical properties comparable to natural hydrogels include liposomes, dendrimers, polymeric micelles, and nanogels …”