Hyaluronic acid-mediated multifunctional iron oxide-based MRI nanoprobes for dynamic monitoring of pancreatic cancer

Abstract

Regarded as the most promising technology for an early and precise detection of pancreatic cancer, a sensitive nanoprobe has been developed to enhance the accumulation of contrast agent at the tumor site. Hyaluronic acid (HA)-mediated multifunctional Fe3O4 nanoparticles (NPs) were used to target pancreatic cancer cells because on their cytomembrane they overexpress CD44, a receptor protein that has a high affinity to HA. The formation of HA-mediated multifunctional Fe3O4 nanoparticles began with the synthesis of polyethyleneimine (PEI·NH2) stabled Fe3O4 NPs by slight reduction. Subsequently, the formed Fe3O4@PEI·NH2 NPs were modified with fluorescein isothiocyanate (FITC), polyethylene glycol (mPEG-COOH) and HA in succession to form the multifunctional Fe3O4 NPs denoted as HA-Fe3O4 NPs. HA served as a targeting molecule to identify the surface antibody of CD44. As nanoparticles with a diameter of ca. 11.9 nm, the HA-Fe3O4 NPs exhibited very high r2 relaxivity of 321.4 mM-1 s-1 and this has proved that HA-Fe3O4 NPs could be efficient T2-weighted magnetic resonance imaging (MRI) contrast agents. In a CCK8 cell proliferation assay of HA-Fe3O4 NPs, there was no toxic response for Fe concentrations up to 100 μg mL-1. Flow cytometry, confocal microscopy observation, and cell MRI results show that the HA-targeted groups had significantly higher cellular uptake than the nontargeted groups. This demonstrates that the HA-Fe3O4 NPs are uptaken by pancreatic cells via an HA-mediated targeting pathway. The HA-mediated active targeting strategy could be applied to other biomedical projects.