A threefold increase in SAR performance for magnetic hyperthermia by compositional tuning in zinc-substituted iron oxide superparamagnetic nanoparticles with superior biocompatibility

In this work, we report a ultrahigh specific absorption rate (SAR) performance in Zn-substituted magnetite superparamagnetic (SPM) nanoparticles (NPs) for potential application in magnetic hyperthermia (MHT)-based cancer treatment. Although MHT shows promise in cancer therapy, challenges such as low heating performance, agglomeration of magnetic nanoparticles (MNPs) in blood veins, cytotoxicity, and hemocompatibility have hindered clinical uses. To overcome these challenges, we adopted a reverse-micelles based coprecipitation synthesis approach to prevent MNPs agglomeration and optimized the substitution of Zn ions in magnetite to enhance heating performance. Calorimetric measurements showed SAR values of 118 W/g and 181 W/g for magnetite NPs using the initial slope method (ISM) and Box Lucas method (BLM), respectively. Through our compositional optimizations, we achieved a significant increase in SAR value by consciously substituting Zn²⁺ ions in the magnetite lattice. Specifically, we obtained SAR values of 325 W/g and 579 W/g (>300% increase) for Zn_0.3Fe_2.7O₄ MNPs using ISM and BLM, respectively. This enhancement can be attributed to improved saturation magnetization (174–257 kA/m) and magneto-crystalline anisotropy (12–24 kJ/m³). The increase in saturation magnetization in the magnetite MNPs can be explained by the higher magnetic moment resulting from increased Zn concentration up to Zn_xFe_3-xO₄(x = 0.3), strengthening the J_AB interaction. However, further increases in Zn concentration lead to a decrease in saturation magnetization due to non-collinearity, as described by the Yafet-Kittle model. Our optimized MNPs exhibit improved heating performance, enabling the use of lower MNPs concentrations for cancer treatment, reducing potential toxicity effects. Biocompatibility investigations demonstrated a low hemolysis rate (<5%) in a hemolysis assay with red blood cells and high cytocompatibility (>92% cell viability) in MTT assays for all compositions, confirming their potential suitability for clinical applications. This study offers a promising approach to enhance SAR performance, addressing MHT-based cancer treatment challenges, and improving clinical suitability.