Superparamagnetic nanohybrids with cross-linked polymers providing higher in vitro stability

Abstract

A simple, rapid, reproducible, and scalable method for generating highly stable cross-linked superparamagnetic nanohybrids was developed. Pre-coating of superparamagnetic iron oxide nanoparticle surfaces with a biocompatible polymer, hydroxy polyvinyl alcohol (PVA-OH) prior to cross-linking with silica precursor resulted in improved stability, uniform morphologies and allows for further surface functionalization. The obtained magnetic nanohybrids contain a non-porous silica layer, are monodisperse (size 50.0 ± 3.7 nm), and show colloidal stability applicable for biomedical applications (pH 7.35–7.45) with long shelf life (>9 months). In vitro studies indicate that as-prepared nanohybrids are non-cytotoxic and highly robust toward endosomal/lysosomal conditions, with no particle dissolution evident for up to 42 days. As a demonstration of the potential utility of these nanohybrids in medical diagnostic applications (e.g., MRI), surface functionalization with folic acid resulted in particle recognition and affinity to folate receptor-positive cervix (HeLa) cells. Accordingly, the facile development of these non-toxic, stable cross-linked magnetic nanohybrids, with the added benefit of scalable preparation, should serve as an entry point for the further development of safer, target specific, MRI contrast agents for cancer diagnosis.