RGDS-functionalized polyethylene glycol hydrogel-coated magnetic iron oxide nanoparticles enhance specific intracellular uptake by HeLa cells

Caner Nazli¹, Tugba Ipek Ergenc², Yasemin Yar¹, Havva Yagci Acar^1,3, Seda Kizilel^1,2
1Graduate School of Sciences and Engineering, Koç University, ²Department of Chemical and Biological Engineering, College of Engineering, Koç University, ³Department of Chemistry, Faculty of Arts and Sciences, Koç University, Istanbul, Turkey

Abstract: The objective of this study was to develop thin, biocompatible, and biofunctional hydrogel-coated small-sized nanoparticles that exhibit favorable stability, viability, and specific cellular uptake. This article reports the coating of magnetic iron oxide nanoparticles (MIONPs) with covalently cross-linked biofunctional polyethylene glycol (PEG) hydrogel. Silanized MIONPs were derivatized with eosin Y, and the covalently cross-linked biofunctional PEG hydrogel coating was achieved via surface-initiated photopolymerization of PEG diacrylate in aqueous solution. The thickness of the PEG hydrogel coating, between 23 and 126 nm, was tuned with laser exposure time. PEG hydrogel-coated MIONPs were further functionalized with the fibronectin-derived arginine-glycine-aspartic acid-serine (RGDS) sequence, in order to achieve a biofunctional PEG hydrogel layer around the nanoparticles. RGDS-bound PEG hydrogel-coated MIONPs showed a 17-fold higher uptake by the human cervical cancer HeLa cell line than that of amine-coated MIONPs. This novel method allows for the coating of MIONPs with nano-thin biofunctional hydrogel layers that may prevent undesirable cell and protein adhesion and may allow for cellular uptake in target tissues in a specific manner. These findings indicate that the further biofunctional PEG hydrogel coating of MIONPs is a promising platform for enhanced specific cell targeting in biomedical imaging and cancer therapy.

Keywords: PEG hydrogel, surface-initiated photopolymerization, nanoparticle encapsulation, agglomeration