Self-Regulated Cobalt–Zinc–Ferrite Nanoprobe for Targeted Chemomagnetic Hyperthermia in Cancer Therapy

Chemo-magnetic hyperthermia is a promising alternative anticancer treatment strategy employed to synergize the therapeutic efficacy of chemotherapy and magnetic hyperthermia. Despite its potential efficacy, most chemo-magnetic hyperthermia strategies are limited owing to limited <i>in vivo</i> thermal conversion ability and inadequate local therapeutic temperatures with nontargeted, uncontrolled release of anticancer agents. Herein, we developed a targeted formulation of anticancer drug-loaded nanoprobe for site-specific chemo-magnetic hyperthermia. The engineered nanoprobe comprising doxorubicin-loaded cobalt-zinc-ferrite nanoparticles, surface-modified with estrone-3-hemisuccinate (TMNPs), exhibits enhanced magnetic properties, including elevated saturation magnetization and the ability to a prolonged constant therapeutic temperature (42-46 °C) under an alternating magnetic field of 20 mT. Targeted delivery was achieved via specific interaction with estrogen receptors (ERs), which resulted in markedly higher apoptosis (∼97%) in ER-positive MCF-7 cells compared to ER-negative controls. <i>In vivo</i> evaluation using a xenograft murine model of breast cancer demonstrated the efficacy of TMNPs in orchestrating a multifaceted therapeutic response through the synergistic integration of chemotherapeutic and hyperthermic modalities. Immunofluorescence analysis of tumor tissues post-treatment revealed the localized induction of thermal stress and upregulation of Heat Shock Protein 70 (HSP-70), a biomarker linked to enhanced immune cell infiltration and activation within the tumor microenvironment. Overall, this study presents a methodical effort to explore the effectiveness of cobalt-zinc-ferrite nanoprobe for chemo-magnetic hyperthermia effects that can be used for efficient, patient-specific, targeted, controlled anticancer therapy through chemodynamic-magnetic-thermal synergistic therapy.