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<p>Cancer therapy continues to face major limitations, including poor tumor selectivity, hypoxia-associated resistance, insufficient reactive oxygen species (ROS) generation, and systemic toxicity of conventional chemotherapeutics. Magnetic nanoparticle-based platforms, particularly manganese ferrite (MnFe<sub>2</sub>O<sub>4</sub>), offer a promising solution due to their intrinsic magnetic responsiveness, catalytic activity, and potential for multifunctional therapeutic integration. However, achieving simultaneous tumor starvation, oxygen (O<sub>2</sub>) modulation, and efficient magnetic hyperthermia within a single nanoplatform remains a critical challenge in cancer nanomedicine. In this study, MnFe<sub>2</sub>O<sub>4</sub> magnetic nanoparticles were synthesized by thermal decomposition method and subsequently functionalized with methoxy polyethylene glycol (mPEG) and glucose oxidase (GOx). Surface modification improved colloidal stability, as reflected by a reduction in hydrodynamic diameter from 184.9&#xa0;nm to 132.6&#xa0;nm and zeta potential shift from − 23.3 to − 26.2 mV after enzymatic conjugation. Under an alternating magnetic field, GOx@mPEG-MnFe<sub>2</sub>O<sub>4</sub> nanoparticles achieved a high specific absorption rate (SAR) of 377&#xa0;W/g, demonstrating efficient magnetic hyperthermia capability. Functionally, the nanoconjugates enabled synergistic therapy through glucose depletion, hydrogen peroxide decomposition with O<sub>2</sub> evolution, hydroxyl radical (•OH) production, and intracellular glutathione depletion. Although overall ROS levels were moderately reduced in the final formulation, the coordinated therapeutic mechanisms significantly enhanced anticancer efficacy. In vitro studies confirmed excellent biocompatibility toward normal cells and 76.56% cytotoxicity against MCF-7 breast cancer cells, achieving up to 90% targeted therapeutic efficiency. This integrated nanoplatform effectively addresses hypoxia, metabolic adaptation, and limited therapeutic synergy, offering a promising strategy for advanced cancer treatment.</p>

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Glucose oxidase conjugated mPEG-MnFe2O4 nanoparticles for advanced chemodynamic, starvation and magnetic hyperthermia based synergistic cancer therapy

  • 期刊论文

  • 发表日期：

    2026年7月13日

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  • S. A. Patil,
  • P. P. Kolekar,
  • M. G. Joshi,
  • A. B. Salunkhe,
  • N. D. Thorat,
  • V. M. Khot

摘要

Cancer therapy continues to face major limitations, including poor tumor selectivity, hypoxia-associated resistance, insufficient reactive oxygen species (ROS) generation, and systemic toxicity of conventional chemotherapeutics. Magnetic nanoparticle-based platforms, particularly manganese ferrite (MnFe2O4), offer a promising solution due to their intrinsic magnetic responsiveness, catalytic activity, and potential for multifunctional therapeutic integration. However, achieving simultaneous tumor starvation, oxygen (O2) modulation, and efficient magnetic hyperthermia within a single nanoplatform remains a critical challenge in cancer nanomedicine. In this study, MnFe2O4 magnetic nanoparticles were synthesized by thermal decomposition method and subsequently functionalized with methoxy polyethylene glycol (mPEG) and glucose oxidase (GOx). Surface modification improved colloidal stability, as reflected by a reduction in hydrodynamic diameter from 184.9 nm to 132.6 nm and zeta potential shift from − 23.3 to − 26.2 mV after enzymatic conjugation. Under an alternating magnetic field, GOx@mPEG-MnFe2O4 nanoparticles achieved a high specific absorption rate (SAR) of 377 W/g, demonstrating efficient magnetic hyperthermia capability. Functionally, the nanoconjugates enabled synergistic therapy through glucose depletion, hydrogen peroxide decomposition with O2 evolution, hydroxyl radical (•OH) production, and intracellular glutathione depletion. Although overall ROS levels were moderately reduced in the final formulation, the coordinated therapeutic mechanisms significantly enhanced anticancer efficacy. In vitro studies confirmed excellent biocompatibility toward normal cells and 76.56% cytotoxicity against MCF-7 breast cancer cells, achieving up to 90% targeted therapeutic efficiency. This integrated nanoplatform effectively addresses hypoxia, metabolic adaptation, and limited therapeutic synergy, offering a promising strategy for advanced cancer treatment.