One-pot preparation of hyaluronic acid-coated iron oxide nanoparticles for magnetic hyperthermia therapy and targeting CD44-overexpressing cancer cells

Abstract

In the present study, a facile one-pot hydrothermal method is introduced for preparation of hyaluronic acid-coated Fe₃O₄ nanoparticles (Fe₃O₄@HA NPs) for theranostic applications. In the proposed method, hyaluronic acid acts simultaneously as a biocompatible coating layer and as a targeting ligand for CD44 receptor overexpressed on the surface of breast cancer cells. The obtained product with narrow hydrodynamic size distribution exhibited a high colloidal stability at physiological pH for more than three months. Cytotoxicity measurements indicated a negligible toxicity of the prepared sample against L929 normal cells. Preferential targeting of Fe₃O₄@HA NPs to CD44-overexpressing cancer cells was studied by comparing the uptake of the prepared nanoparticles by MDA-MB-231 cancer cells (positive CD44 expression) and L929 normal cells (negative CD44 expression). Uptake of the Fe₃O₄@HA NPs by MDA-MB-231 cells was found to be 4-fold higher than the normal cells. Also, the in vitro analysis showed that, the uptake of Fe₃O₄@HA NPs by MDA-MB-231 breast cancer cells is significantly enhanced as compared to non-targeted dextran-coated Fe₃O₄ NPs. Moreover, the heat generation capability of the Fe₃O₄@HA NPs for magnetic hyperthermia application was studied by exposing the prepared nanoparticles to different safe alternating magnetic fields (f = 120 kHz, H = 8, 10, and 12 kA/m). The intrinsic loss power obtained for Fe₃O₄@HA NPs was about 3.5 nHm²/kg, which is about 25-fold larger than that of obtained for commercial available Fe₃O₄ nanoparticles for biomedical applications. Good colloidal stability, biocompatibility, high heating efficacy, and targeting specificity to CD44 receptor-overexpressing cancer cells could make the Fe₃O₄@HA NPs as a promising multifunctional platform for diagnosis and therapeutic applications.

Keywords: Active targeting; CD44 receptor; Fe(3)O(4) nanoparticles; Hyaluronic acid; Hyaluronic acid coated iron oxide; Magnetic hyperthermia.