Hyaluronic acid conjugated superparamagnetic iron oxide nanoparticle for cancer diagnosis and hyperthermia therapy

Abstract

Recently, superparamagnetic iron oxide nanoparticles (SPIONs) have been prepared for magnetic resonance (MR) imaging and hyperthermia therapy. Here, we have developed hyaluronic acid (HA) coated SPIONs primarily for use in a hyperthermia application with an MR diagnostic feature with hydrodynamic size measurement of 176nm for HA-PEG10-SPIONs and 149nm for HA-SPIONs. HA-coated SPIONs (HA-SPIONs) were prepared to target CD44-expressed cancer where the carrier was conjugated to PEG for analyzing longer circulation in blood as well as for biocompatibility (HA-PEG10 SPIONs). Characterization was conducted with TEM (shape), DLS (size), ELS (surface charge), TGA (content of polymer) and MRI (T2-relaxation time). The heating ability of both the HA-SPIONs and HA-PEG10-SPIONs was studied by AMF and SAR calculation. Cellular level tests were conducted using SCC7 and NIH3T3 cell lines to confirm cell viability and cell specific uptake. HA-SPIONs and HA-PEG10-SPIONs were injected to xenograft mice bearing the SCC7 cell line for MRI cancer diagnosis. We found that HA-SPION-injected mice tumors showed nearly 40% MR T2 contrast compared to the 20% MR T2 contrast of the HA-PEG10-SPION group over a 3h time period. Finally, in vitro hyperthermia studies were conducted in the SCC7 cell line that showed less than 40% cell viability for both HA-SPIONs and HA-PEG10-SPIONs in AMF treated cells. In conclusion, HA-SPIONs were targeted specifically to the CD44, and the hyperthermia effect of HA-SPIONs and HA-PEG10-SPIONs was found to be significant for future studies.

Keywords: Hyaluronic acid (HA); Hyperthermia; Magnetic resonance imaging (MRI); SPION.