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Improving the Cellular Uptake of Biomimetic Magnetic Nanoparticles

Magnetococcus marinus magnetosome-associated protein MamC, expressed as recombinant, has been proven to mediate the formation of novel biomimetic magnetic nanoparticles (BMNPs) that are successful drug nanocarriers for targeted chemotherapy and hyperthermia agents. These BMNPs present several advant...

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Autores principales: Vurro, Federica, Jabalera, Ylenia, Mannucci, Silvia, Glorani, Giulia, Sola-Leyva, Alberto, Gerosa, Marco, Romeo, Alessandro, Romanelli, Maria Grazia, Malatesta, Manuela, Calderan, Laura, Iglesias, Guillermo R., Carrasco-Jiménez, María P., Jimenez-Lopez, Concepcion, Perduca, Massimiliano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002967/
https://www.ncbi.nlm.nih.gov/pubmed/33803544
http://dx.doi.org/10.3390/nano11030766
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author Vurro, Federica
Jabalera, Ylenia
Mannucci, Silvia
Glorani, Giulia
Sola-Leyva, Alberto
Gerosa, Marco
Romeo, Alessandro
Romanelli, Maria Grazia
Malatesta, Manuela
Calderan, Laura
Iglesias, Guillermo R.
Carrasco-Jiménez, María P.
Jimenez-Lopez, Concepcion
Perduca, Massimiliano
author_facet Vurro, Federica
Jabalera, Ylenia
Mannucci, Silvia
Glorani, Giulia
Sola-Leyva, Alberto
Gerosa, Marco
Romeo, Alessandro
Romanelli, Maria Grazia
Malatesta, Manuela
Calderan, Laura
Iglesias, Guillermo R.
Carrasco-Jiménez, María P.
Jimenez-Lopez, Concepcion
Perduca, Massimiliano
author_sort Vurro, Federica
collection PubMed
description Magnetococcus marinus magnetosome-associated protein MamC, expressed as recombinant, has been proven to mediate the formation of novel biomimetic magnetic nanoparticles (BMNPs) that are successful drug nanocarriers for targeted chemotherapy and hyperthermia agents. These BMNPs present several advantages over inorganic magnetic nanoparticles, such as larger sizes that allow the former to have larger magnetic moment per particle, and an isoelectric point at acidic pH values, which allows both the stable functionalization of BMNPs at physiological pH value and the molecule release at acidic (tumor) environments, simply based on electrostatic interactions. However, difficulties for BMNPs cell internalization still hold back the efficiency of these nanoparticles as drug nanocarriers and hyperthermia agents. In the present study we explore the enhanced BMNPs internalization following upon their encapsulation by poly (lactic-co-glycolic) acid (PLGA), a Food and Drug Administration (FDA) approved molecule. Internalization is further optimized by the functionalization of the nanoformulation with the cell-penetrating TAT peptide (TATp). Our results evidence that cells treated with the nanoformulation [TAT-PLGA(BMNPs)] show up to 80% more iron internalized (after 72 h) compared to that of cells treated with BMNPs (40%), without any significant decrease in cell viability. This nanoformulation showing optimal internalization is further characterized. In particular, the present manuscript demonstrates that neither its magnetic properties nor its performance as a hyperthermia agent are significantly altered due to the encapsulation. In vitro experiments demonstrate that, following upon the application of an alternating magnetic field on U87MG cells treated with BMNPs and TAT-PLGA(BMNPs), the cytotoxic effect of BMNPs was not affected by the TAT-PLGA enveloping. Based on that, difficulties shown in previous studies related to poor cell uptake of BMNPs can be overcome by the novel nanoassembly described here.
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spelling pubmed-80029672021-03-28 Improving the Cellular Uptake of Biomimetic Magnetic Nanoparticles Vurro, Federica Jabalera, Ylenia Mannucci, Silvia Glorani, Giulia Sola-Leyva, Alberto Gerosa, Marco Romeo, Alessandro Romanelli, Maria Grazia Malatesta, Manuela Calderan, Laura Iglesias, Guillermo R. Carrasco-Jiménez, María P. Jimenez-Lopez, Concepcion Perduca, Massimiliano Nanomaterials (Basel) Article Magnetococcus marinus magnetosome-associated protein MamC, expressed as recombinant, has been proven to mediate the formation of novel biomimetic magnetic nanoparticles (BMNPs) that are successful drug nanocarriers for targeted chemotherapy and hyperthermia agents. These BMNPs present several advantages over inorganic magnetic nanoparticles, such as larger sizes that allow the former to have larger magnetic moment per particle, and an isoelectric point at acidic pH values, which allows both the stable functionalization of BMNPs at physiological pH value and the molecule release at acidic (tumor) environments, simply based on electrostatic interactions. However, difficulties for BMNPs cell internalization still hold back the efficiency of these nanoparticles as drug nanocarriers and hyperthermia agents. In the present study we explore the enhanced BMNPs internalization following upon their encapsulation by poly (lactic-co-glycolic) acid (PLGA), a Food and Drug Administration (FDA) approved molecule. Internalization is further optimized by the functionalization of the nanoformulation with the cell-penetrating TAT peptide (TATp). Our results evidence that cells treated with the nanoformulation [TAT-PLGA(BMNPs)] show up to 80% more iron internalized (after 72 h) compared to that of cells treated with BMNPs (40%), without any significant decrease in cell viability. This nanoformulation showing optimal internalization is further characterized. In particular, the present manuscript demonstrates that neither its magnetic properties nor its performance as a hyperthermia agent are significantly altered due to the encapsulation. In vitro experiments demonstrate that, following upon the application of an alternating magnetic field on U87MG cells treated with BMNPs and TAT-PLGA(BMNPs), the cytotoxic effect of BMNPs was not affected by the TAT-PLGA enveloping. Based on that, difficulties shown in previous studies related to poor cell uptake of BMNPs can be overcome by the novel nanoassembly described here. MDPI 2021-03-18 /pmc/articles/PMC8002967/ /pubmed/33803544 http://dx.doi.org/10.3390/nano11030766 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Vurro, Federica
Jabalera, Ylenia
Mannucci, Silvia
Glorani, Giulia
Sola-Leyva, Alberto
Gerosa, Marco
Romeo, Alessandro
Romanelli, Maria Grazia
Malatesta, Manuela
Calderan, Laura
Iglesias, Guillermo R.
Carrasco-Jiménez, María P.
Jimenez-Lopez, Concepcion
Perduca, Massimiliano
Improving the Cellular Uptake of Biomimetic Magnetic Nanoparticles
title Improving the Cellular Uptake of Biomimetic Magnetic Nanoparticles
title_full Improving the Cellular Uptake of Biomimetic Magnetic Nanoparticles
title_fullStr Improving the Cellular Uptake of Biomimetic Magnetic Nanoparticles
title_full_unstemmed Improving the Cellular Uptake of Biomimetic Magnetic Nanoparticles
title_short Improving the Cellular Uptake of Biomimetic Magnetic Nanoparticles
title_sort improving the cellular uptake of biomimetic magnetic nanoparticles
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002967/
https://www.ncbi.nlm.nih.gov/pubmed/33803544
http://dx.doi.org/10.3390/nano11030766
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