Clinical Translation of Functional Magnetic Nanoparticles for Intracellular Hyperthermia and Cancer Immunotherapy

Sep 22, 2026

Magnetic hyperthermia, where magnetic nanoparticles (MNPs) generate heat under an alternating magnetic field, is presented as a leading cancer-therapy strategy. Direct intratumoral delivery is highlighted for its clinical progress, enabling localized heating while mitigating limited tumor accumulation seen with systemic delivery. Functional MNPs with efficient cellular interaction and intracellular localization extend hyperthermia toward intracellular action and cancer immunotherapy. The review connects nanoparticle engineering to improved intratumoral retention, intracellular delivery, thermal-dose optimization, and therapeutic outcomes.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages20

Reading Time50 min

AccessFree to download

Introduction

Cancer therapy challenges

Hyperthermia as a cancer treatment

Limits of conventional hyperthermia

Graphical Abstract

Evolution toward intracellular therapy

International Journal of Nanomedicine Open Access Full Text Article REVIEW Clinical Translation of Functional Magnetic Nanoparticles for Intracellular Hyperthermia and Cancer Immunotherapy Takeru Fukushima, Masahiro Kaneko , Akira Ito Department of Chemical Systems Engineering, School of Engineering, Nagoya University, Nagoya, 464-8603, Japan Correspondence: Akira Ito, Department of Chemical Systems Engineering, School of Engineering, Nagoya University, Nagoya, 464-8603, Japan, Tel +81527893374, Email [ito.akira@material.nagoya-u.ac.jp](ito.akira@material.nagoya-u.ac.jp) Abstract: Magnetic hyperthermia, in which magnetic nanoparticles (MNPs) generate heat under an alternating magnetic field, has emerged as a promising strategy for cancer therapy. Among numerous magnetic hyperthermia platforms, direct intratumoral administration has achieved the greatest clinical progress because it enables localized heat generation while overcoming the limited tumor accumulation associated with systemic nanoparticle delivery. The development of functional MNPs capable of efficient cellular interaction and intracellular localization has further expanded magnetic hyperthermia beyond conventional tissue heating toward intracellular hyperthermia and cancer immunotherapy. This review summarizes the historical evolution and clinical translation of functional MNPs with particular emphasis on the design principles that have facilitated successful clinical development. We discuss how advances in nanoparticle engineering have improved intratumoral retention, intracellular delivery, thermal dose optimization, and therapeutic efficacy. We further review the emerging role of magnetic hyperthermia as an in situ vaccination strategy capable of inducing immunogenic cell death and stimulating systemic antitumor immunity, providing a biological rationale for combination with immunotherapies. Finally, we discuss current challenges limiting widespread clinical translation, together with future perspectives on multifunctional therapeutic and theranostic nanoplatforms. These advances position functional MNPs as promising platforms for nextgeneration cancer therapy. Keywords: magnetic hyperthermia, magnetic nanoparticles, alternating magnetic field, cancer therapy, nanomedicine Introduction Cancer remains one of the leading causes of death worldwide despite substantial advances in surgery, radiotherapy, chemotherapy, molecularly targeted therapy, and immunotherapy. Although these therapeutic modalities have significantly improved patient outcomes, the treatment of advanced, recurrent, and metastatic cancers remains a major clinical challenge. Consequently, there remains a need for innovative therapeutic strategies that selectively eradicate tumor cells while minimizing damage to normal tissues. Hyperthermia, the therapeutic elevation of tumor temperature, has long been recognized as a promising approach for cancer treatment. Tumor cells are generally more susceptible to heat-induced damage than normal tissues because of their abnormal vasculature, altered metabolism, and impaired ability to dissipate heat.1 Conventional hyperthermia techniques, including radiofrequency, microwave, ultrasound, and capacitive heating systems, have demonstrated therapeutic benefits.2 However, precise and selective heating of tumors remains difficult because thermal energy is often deposited over a broad region, resulting in insufficient heating of the target tissue and unintended heating of surrounding normal tissues. [https://doi.org/10.2147/IJN.S629846](https://doi.org/10.2147/IJN.S629846) [Received: 10 July 2026](Received: 10 July 2026) [Accepted: 6 August 2026](Accepted: 6 August 2026) [Published: 21 August 2026](Published: 21 August 2026) International Journal of Nanomedicine 2026:21 629846 1 © 2026 Fukushima et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at [https://www.dovep

FAQs

Why is direct intratumoral administration important for clinical translation of magnetic hyperthermia?

It enables localized heat generation within the tumor while avoiding the limited accumulation and associated constraints of systemic nanoparticle delivery.

How do functional magnetic nanoparticles change hyperthermia from tissue heating to intracellular hyperthermia and immunotherapy?

They are designed for efficient cellular interaction and intracellular localization, expanding hyperthermia beyond heating of bulk tissue toward intracellular effects and cancer immunotherapy.

What are the main challenges that hinder widespread clinical translation of functional MNPs?

Current limitations are discussed as barriers to broader clinical adoption, alongside future perspectives for multifunctional therapeutic and theranostic nanoplatforms.

Sep 22, 2026

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