Poly(N-acryloylmorpholine) Nanogels as Promising Materials for Biomedical Applications: Low Protein Adhesion and High Colloidal Stability

Poly(N-acryloylmorpholine) (P(NAM))-based materials have been developed to prevent protein adhesion to surfaces due to their biocompatibility and protein-repellent properties. However, transferring the benefits of P(NAM) to nanoscale materials such as nanogels has not yet been studied. This can be attributed to the challenging colloidal synthesis of such particles with highly hydrophilic networks. To address this challenge, we have developed an inverse miniemulsion approach for free radical polymerization of NAM in dispersed nanodroplets. This strategy allows preparation of well-defined P(NAM) nanogels with a controllable size (250-350 nm). To impart additional functionality, our approach can easily be adapted to include ionic co-monomers and degradable cross-linkers. The resulting pH-responsive swelling and redox-triggered degradation profiles were demonstrated by dynamic light scattering measurements. To test the influence of such additional functionality on the protein-repellent properties, protein adsorption on the nanogels was assessed. For surface-immobilized nanogels, reduced unspecific binding of albumin was demonstrated for all nanogels via fluorescence microscopy. For nanogels in suspension, nanoparticle tracking analysis showed no increase in nanogel size upon incubation in serum and plasma, thus suggesting limited protein adsorption and colloidal high stability for over 2 months. Finally, cytotoxicity essays demonstrated the potential of these materials for bio-applications. Overall, these results suggest that biocompatibility and protein-repellent properties of P(NAM) can be transferred to nanogels and are maintained upon integration of additional chemical functionality. Thus, our synthetic strategy builds the foundation for utilizing such versatile colloidal materials in biomedical applications, e.g., as versatile drug delivery systems.