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Nanomaterials 2018, 8(7), 468; https://doi.org/10.3390/nano8070468

Combined Treatments of Magnetic Intra-Lysosomal Hyperthermia with Doxorubicin Promotes Synergistic Anti-Tumoral Activity

INSERM ERL1226—Receptology and Therapeutic Targeting of Cancers, Laboratoire de Physique et Chimie des Nano-Objets, CNRS UMR5215-INSA, Université de Toulouse III, F-31432 Toulouse, France
These authors contributed equally to this work.
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Received: 30 May 2018 / Revised: 14 June 2018 / Accepted: 19 June 2018 / Published: 27 June 2018
(This article belongs to the Special Issue Magnetic Nanoparticles in Biological Applications)
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Abstract

Doxorubicin is a cytotoxic drug used for the treatment of many cancer types. However, its significant dose-related adverse effects including cardiotoxicity may hamper its efficiency. Moreover, the multidrug resistance that appears during treatments limits anti-cancer therapies. Hyperthermia has been introduced as an adjuvant anti-cancer therapy and presents promising opportunities especially in combination with chemotherapy. However, hyperthermia methods including standard magnetic hyperthermia do not discriminate between the target and the surrounding normal tissues and can lead to side effects. In this context, a Magnetic Intra-Lysosomal Hyperthermia (MILH) approach, which occurs without perceptible temperature rise, has been developed. We previously showed that minute amounts of iron oxide magnetic nanoparticles targeting the gastrin receptor (CCK2R) are internalized by cancer cells through a CCK2R-dependent physiological process, accumulated into their lysosomes and kill cancer cells upon high frequency alternating magnetic field (AMF) application through lysosomal cell death. Here, we show that the combination of MILH with doxorubicin increases the efficiency of the eradication of endocrine tumor cells with synergism. We also demonstrate that these two treatments activate two different cell death pathways that are respectively dependent on Caspase-1 and Caspase-3 activation. These findings will result in the development of new anti-tumoral, intra-lysosomal-thermo/chemotherapy with better curative effects than chemotherapy alone and that are devoid of adverse effects linked to standard hyperthermia approaches. View Full-Text
Keywords: magnetic nanoparticles; magnetic hyperthermia; cell death; cancer; endocrine tumors; doxorubicin magnetic nanoparticles; magnetic hyperthermia; cell death; cancer; endocrine tumors; doxorubicin
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El Hajj Diab, D.; Clerc, P.; Serhan, N.; Fourmy, D.; Gigoux, V. Combined Treatments of Magnetic Intra-Lysosomal Hyperthermia with Doxorubicin Promotes Synergistic Anti-Tumoral Activity. Nanomaterials 2018, 8, 468.

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