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.
