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Article

Biomimetic Magnetite Nanoparticles as Targeted Drug Nanocarriers and Mediators of Hyperthermia in an Experimental Cancer Model

1
Department of Health Sciences, Università del Piemonte Orientale A. Avogadro, Via Solaroli 17, 28100 Novara, Italy
2
Department of Microbiology, University of Granada, Campus Fuentenueva, s/n, 18071 Granada, Spain
3
Department of Translational Medicine, Università del Piemonte Orientale A. Avogadro, Via Solaroli 17, 28100 Novara, Italy
4
Department of Applied Physic, University of Granada, Campus Fuentenueva, s/n, 18071 Granada, Spain
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Centro di Biotecnologie per la Ricerca Medica Applicata (BRMA), Via Solaroli 17, 28100 Novara, Italy
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Consorzio Interuniversitario per Biotecnologie (CIB), Località Padriciano 99, 34149 Area di Ricerca, Trieste, Italy
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Consorzio Interuniversitario Nazionale per la Scienza e Tecnologia dei Materiali (INSTM), Via Giuseppe Giusti 9, 50121 Firenze, Italy
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Consorzio Interuniversitario di Ricerca in Chimica dei Metalli nei Sistemi Biologici (CIRCMSB) Piazza Umberto I 1, 70121 Bari, Italy
9
Centro Interdipartimentale di Medicina Rigenerativa (CIMeR), Via Montpellier, 1, 00133 Roma, Italy
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Present Address: Department of Microbiology, Facultad de Ciencias, Universidad de Granada, Campus Fuentenueva, s/n, 18071 Granada, Spain.
Cancers 2020, 12(9), 2564; https://doi.org/10.3390/cancers12092564
Received: 5 August 2020 / Revised: 3 September 2020 / Accepted: 3 September 2020 / Published: 9 September 2020
(This article belongs to the Collection Cancer Nanomedicine)
The application of simultaneous and different strategies to treat cancer appears a promising therapeutic approach. Herein we proposed the application of chemotherapy combined with a magnetic nanocarrier delivery system to an in vitro and an in vivo experimental mammary carcinoma model. Drug-loaded biomimetic magnetic nanoparticle can be directed and concentrated on the tumor cells or site by the apposition of a magnet. Moreover, these nanoparticles can respond to an alternating magnetic field by developing hyperthermia around 43 °C, a temperature at which tumor cells, but not healthy cells, are particularly sensitive and thus induced to death. Indeed, when this nanoformulation is injected in vivo in the tumor site, and hyperthermia is generated, the combined chemo-thermal therapy mediated by these drug-loaded magnetic nanoparticles have a stronger therapeutic benefit compared to that carried out by the chemotherapeutic alone. These nanoformulation and strategy are thus promising tools for translational applications in cancer therapy.
Biomimetic magnetic nanoparticles mediated by magnetosome proteins (BMNPs) are potential innovative tools for cancer therapy since, besides being multifunctional platforms, they can be manipulated by an external gradient magnetic field (GMF) and/or an alternating magnetic field (AMF), mediating targeting and hyperthermia, respectively. We evaluated the cytocompatibility/cytotoxicity of BMNPs and Doxorubicin (DOXO)-BMNPs in the presence/absence of GMF in 4T1 and MCF-7 cells as well as their cellular uptake. We analyzed the biocompatibility and in vivo distribution of BMNPs as well as the effect of DOXO-BMNPs in BALB/c mice bearing 4T1 induced mammary carcinomas after applying GMF and AMF. Results: GMF enhanced the cell uptake of both BMNPs and DOXO-BMNPs and the cytotoxicity of DOXO-BMNPs. BMNPs were biocompatible when injected intravenously in BALB/c mice. The application of GMF on 4T1 tumors after each of the repeated (6×) iv administrations of DOXO-BMNPs enhanced tumor growth inhibition when compared to any other treatment, including that with soluble DOXO. Moreover, injection of DOXO-BMNPs in the tumor combined with application of an AMF resulted in a significant tumor weight reduction. These promising results show the suitability of BMNPs as magnetic nanocarriers for local targeted chemotherapy and as local agents for hyperthermia. View Full-Text
Keywords: magnetic nanoparticles; tumor targeting; cytotoxicity; doxorubicin; hyperthermia magnetic nanoparticles; tumor targeting; cytotoxicity; doxorubicin; hyperthermia
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MDPI and ACS Style

Oltolina, F.; Peigneux, A.; Colangelo, D.; Clemente, N.; D’Urso, A.; Valente, G.; Iglesias, G.R.; Jiménez-Lopez, C.; Prat, M. Biomimetic Magnetite Nanoparticles as Targeted Drug Nanocarriers and Mediators of Hyperthermia in an Experimental Cancer Model. Cancers 2020, 12, 2564. https://doi.org/10.3390/cancers12092564

AMA Style

Oltolina F, Peigneux A, Colangelo D, Clemente N, D’Urso A, Valente G, Iglesias GR, Jiménez-Lopez C, Prat M. Biomimetic Magnetite Nanoparticles as Targeted Drug Nanocarriers and Mediators of Hyperthermia in an Experimental Cancer Model. Cancers. 2020; 12(9):2564. https://doi.org/10.3390/cancers12092564

Chicago/Turabian Style

Oltolina, Francesca, Ana Peigneux, Donato Colangelo, Nausicaa Clemente, Annarita D’Urso, Guido Valente, Guillermo R. Iglesias, Concepcion Jiménez-Lopez, and Maria Prat. 2020. "Biomimetic Magnetite Nanoparticles as Targeted Drug Nanocarriers and Mediators of Hyperthermia in an Experimental Cancer Model" Cancers 12, no. 9: 2564. https://doi.org/10.3390/cancers12092564

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