Long Term Toxicity of Silica Coated Iron Oxide Nanocrystalline Clusters used for Magnetic Hyperthermia Applications

Abstract Superparamagnetic iron oxide nanocrystalline clusters (IONC) have gained significant attention in biomedical applications for their unique properties and functionalities. The biomedical field has harnessed the potential of IONCs for various applications, including diagnostics, drug delivery, imaging, and hyperthermia therapy. The interactions of the nanomaterials with the cells, tissues, and microenvironment can reveal the biocompatibility or harmful effects in biological systems therefore a systematic understanding of the toxicity parameters of these materials are essential. The Fe₃O₄ nanocrystalline clusters were synthesised by solvothermal process and characterized using XRD, TEM, SEM, and DLS. The in vitro cytotoxicity was assessed on HeLa and MCF-7 cell lines and in vivo toxicity on Swiss albino mice. The average size of synthesized nanocrystalline clusters were found to be 230 nm from TEM analysis. The IONC exhibits promising efficiency for magnetic hyperthermia, with SAR value of 104.1 W/g and intrinsic loss parameter of 1.05 nH m²/Kg⁻¹. The particles did not exhibit significant toxicity when tested on the 2 cell lines. In vivo CBC and serum values were within normal limits at 24 hours, 5- and 75-weeks’ of sacrifice except for considerable increase in SGOT values, but fell back to the normal values during 5- and 75-weeks’ time point. There was a dose-dependent iron accumulation in the liver, spleen, and lungs that was evident in Perl’s histopathological evaluation with liver and spleen being the primary sites for iron metabolism. Residual concentration of IONC was seen in lungs in the 75-weeks animals with minimal changes in the tissue architecture. The result from the current study reveals that the synthesized Si-IONC can be efficiently used for hyperthermia application as they do not show any significant in vitro and in vivo toxicity.