Self-Regulated Magnetic Hyperthermia Using Novel Curie-Temperature-Tuned Nanomaterials: A Multi-Phase Approach to Targeted Cancer Therapy

Archil Chirakadze; Nodar Mitagvaria; Neli Makhviladze; Teimuraz Chubinishvili; Nodar Sulashvili; Omolola Daniel Ademilade Oluwasemilore; Atheena Philip Renny; Vineeta Anish; Dhartiben Patel; Mohammad Al Maarrawi; Giorgi Palavandishvili; Khtuna Tserodze; Kakha Gorgadze; Nana khuskivadze; David Aphkhazava

Authors

Archil Chirakadze PhD, Georgian Technical University Institute "Techinform", Tbilisi, Georgia, Georgian Technical University Institute of Cybernetics, Tbilisi, Georgia, Ivane Javakhishvili Tbilisi State University Institute of Physics, Tbilisi, Georgia
Nodar Mitagvaria Ivane Beritasvili Center of Eperimental Biomedicine, Tbilisi, Georgia
Neli Makhviladze Georgian Techical University, Tbilisi, Georgia
Teimuraz Chubinishvili Georgian Techical University, Tbilisi, Georgia
Nodar Sulashvili MD, PhD, Doctor of Pharmaceutical and Pharmacological Sciences In Medicine, Invited Lecturer (Professor) of Scientific Research-Skills Center at Tbilisi State Medical University; Professor of Medical and Clinical Pharmacology of International School of Medicine at Alte University; Professor of Pharmacology of Faculty of Medicine at Georgian National University SEU, Associate Affiliated Professor of Medical Pharmacology of Faculty of Medicine at Sulkhan-Saba Orbeliani University; Associate Professor of Medical Pharmacology at School of Medicine at David Aghmashenebeli University of Georgia; Associate Professor of Biochemistry and Pharmacology Direction of School of Health Sciences at the University of Georgia. Associate Professor of Pharmacology of Faculty of Dentistry and Pharmacy at Tbilisi Humanitarian Teaching University; Tbilisi, Georgia; Orcid: https://orcid.org/0000-0002-9005-8577
Omolola Daniel Ademilade Oluwasemilore Alte University, Tbilisi, Georgia
Atheena Philip Renny University of Georgia, Tbilisi, Georgia
Vineeta Anish University of Georgia, Tbilisi, Georgia
Dhartiben Patel Alte University, Tbilisi, Georgia
Mohammad Al Maarrawi Alte University, Tbilisi, Georgia
Giorgi Palavandishvili Georgian Techical University, Tbilisi, Georgia
Khtuna Tserodze Georgian Techical University, Tbilisi, Georgia
Kakha Gorgadze Georgian Techical University, Tbilisi, Georgia
Nana khuskivadze Georgian Techical University, Tbilisi, Georgia
David Aphkhazava PhD, Invited Professor of University of Georgia, Tbilisi, Georgia, Orcid: https://orcid.org/0000-0001-6216-6477

Keywords:

Magnetic hyperthermia, Self-regulated nanoparticles, Curie temperature, Ni-Cu nanoalloys, La₁₋ₓAgₓMnO₃ perovskites, Cancer therapy, Microwave synthesis, Zinc phosphate coating, Biocompatibility, Thermotherapy, Nanomedicine, Targeted drug delivery, Toxicity assessment, Behavioral neuroscience, Thermal ablation, Magnetic nanoparticles, Hyperthermia treatment, Cancer nanotechnology, Theranostics, Translational medicine

Abstract

Cancer remains one of the leading causes of mortality worldwide, necessitating the development of innovative therapeutic approaches with enhanced selectivity and reduced systemic toxicity. This study presents a comprehensive investigation into the development and characterization of novel nanomaterials designed for self-regulated magnetic hyperthermia treatment of malignant cells. We synthesized two distinct classes of thermally responsive nanoparticles: Ni-Cu nanoalloys and La₁₋ₓAgₓMnO₃ perovskite structures, both engineered to exhibit Curie temperatures within the therapeutic window of 39-46°C.

The research employed both conventional thermal synthesis and innovative microwave-enhanced methodologies, with systematic incorporation of hydrazine and ammonium chloride as activating agents to optimize particle morphology and magnetic properties. To enhance biocompatibility and stability, nanoparticles were coated with zinc phosphate (Zn₃(PO₄)₂) and carbon shells, creating a protective barrier that minimizes cytotoxic interactions while maintaining thermal responsivity.

Comprehensive toxicological assessment was conducted using established behavioral neuroscience protocols, including multi-branch maze learning paradigms and elevated plus-maze anxiety models, alongside open-field locomotor activity analysis. These assessments were performed both under baseline conditions and during magnetic hyperthermia activation to evaluate potential neurotoxic effects and systemic safety profiles.

Physical characterization revealed that microwave-synthesized nanoparticles demonstrated superior size uniformity (coefficient of variation <15%) and narrower Curie temperature distributions compared to conventionally prepared materials. The La₁₋ₓAgₓMnO₃ system exhibited particularly promising self-regulation capabilities, with heating efficiency of 245 W/g at therapeutic field strengths (H = 300 Oe, f = 300 kHz) while maintaining temperature stability within ±0.8°C of the target threshold.

Pilot-scale synthesis protocols were successfully developed, yielding materials with reproducible magnetic properties and demonstrating scalability potential for clinical translation. In vitro hyperthermia experiments using HeLa and MCF-7 cancer cell lines showed selective cytotoxicity enhancement of 3.2-fold compared to healthy fibroblasts, attributed to the precise temperature control enabled by the Curie-point self-regulation mechanism.

This work establishes a robust framework for the rational design of self-regulating magnetic hyperthermia agents, integrating materials synthesis optimization, comprehensive safety evaluation, and therapeutic efficacy assessment. The developed nanomaterials represent a promising platform for localized cancer treatment with inherent safety mechanisms that prevent thermal overtreatment, addressing a critical limitation of conventional hyperthermia approaches

Self-Regulated Magnetic Hyperthermia Using Novel Curie-Temperature-Tuned Nanomaterials: A Multi-Phase Approach to Targeted Cancer Therapy

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