Origin of Fe ions in ROS production induced in magnetic hyperthermia anti-cancer nanotherapy: release from iron oxide nanoparticles or not?
Abstract
The first and critical reaction in magnetic hyperthermia to induce the death of cancer cells is the production of ROS (reactive oxygen species). We previously showed that it is possible to specifically deliver iron oxide magnetic nanoparticles (IONPs) in the lysosomes of cancer cells and eradicate them by targeted magnetic intra-lysosomal hyperthermia (MILH) via the application of a high frequency alternating magnetic field (AMF) without macroscopic temperature elevation. The mechanism involves a local temperature elevation at the IONPs surface which enhances the ROS production through the Fenton reaction; ROS then peroxide the proteins and lipids of the lysosomal membrane, inducing its permeabilization and leading to lysosomal enzymes release and cell death. Fe ions, critical to produce ROS in MILH, were assumed to be released by IONPs. We thus developed PEGylated multi-cores IONPs called NanoFlowers (NF@PEG) presenting or not a SiO 2 shell (NF@SiO 2 @PEG), the later preventing the Fe 3+ release from IONPs. NF@PEG released Fe ions and produced ROS production in vitro , in acidic medium mimicking lysosome upon AMF exposure, whereas NF@SiO 2 @PEG did not. Surprisingly, both nanoparticles increased the ROS production in cells, induced lysosome permeabilization and cell death, and slowed down the proliferation of cancer cells with the same efficacy, upon AMF application, indicating that MILH was efficient in absence of Fe 3+ release from IONPs. In contrast, Ferristatin-II, an iron uptake inhibitor, prevented the ROS production and cell death in MILH induced by both IONPs, elucidating the role of endogenous iron cations responsible for the ROS production ROS in MILH to kill cancer cells.
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BibTeX
@misc{journauxduclos2026origin,
title = {{Origin of Fe ions in ROS production induced in magnetic hyperthermia anti-cancer nanotherapy: release from iron oxide nanoparticles or not?}},
author = {Justine Journaux-Duclos and Megi Bejko and Pascal Clerc and Yasmina Al Yaman and Ahmed Abdelhamid and Géraldine Ballon and Corinne Bousquet and Julian Carrey and Stéphane Mornet and Olivier Sandre and Véronique Gigoux},
howpublished = {HAL},
year = {2026},
month = jul,
doi = {10.64898/2026.07.06.736751},
url = {https://u-bordeaux.hal.science/hal-05765933v1},
note = {CC BY-SA 4.0},
}
RIS
TY - UNPB
TI - Origin of Fe ions in ROS production induced in magnetic hyperthermia anti-cancer nanotherapy: release from iron oxide nanoparticles or not?
AU - Justine Journaux-Duclos
AU - Megi Bejko
AU - Pascal Clerc
AU - Yasmina Al Yaman
AU - Ahmed Abdelhamid
AU - Géraldine Ballon
AU - Corinne Bousquet
AU - Julian Carrey
AU - Stéphane Mornet
AU - Olivier Sandre
AU - Véronique Gigoux
PY - 2026
DA - 2026/07/08
PB - HAL
DO - 10.64898/2026.07.06.736751
UR - https://u-bordeaux.hal.science/hal-05765933v1
AB - The first and critical reaction in magnetic hyperthermia to induce the death of cancer cells is the production of ROS (reactive oxygen species). We previously showed that it is possible to specifically deliver iron oxide magnetic nanoparticles (IONPs) in the lysosomes of cancer cells and eradicate them by targeted magnetic intra-lysosomal hyperthermia (MILH) via the application of a high frequency alternating magnetic field (AMF) without macroscopic temperature elevation. The mechanism involves a local temperature elevation at the IONPs surface which enhances the ROS production through the Fenton reaction; ROS then peroxide the proteins and lipids of the lysosomal membrane, inducing its permeabilization and leading to lysosomal enzymes release and cell death. Fe ions, critical to produce ROS in MILH, were assumed to be released by IONPs. We thus developed PEGylated multi-cores IONPs called NanoFlowers (NF@PEG) presenting or not a SiO 2 shell (NF@SiO 2 @PEG), the later preventing the Fe 3+ release from IONPs. NF@PEG released Fe ions and produced ROS production in vitro , in acidic medium mimicking lysosome upon AMF exposure, whereas NF@SiO 2 @PEG did not. Surprisingly, both nanoparticles increased the ROS production in cells, induced lysosome permeabilization and cell death, and slowed down the proliferation of cancer cells with the same efficacy, upon AMF application, indicating that MILH was efficient in absence of Fe 3+ release from IONPs. In contrast, Ferristatin-II, an iron uptake inhibitor, prevented the ROS production and cell death in MILH induced by both IONPs, elucidating the role of endogenous iron cations responsible for the ROS production ROS in MILH to kill cancer cells.
ER -