Design and Validation of Nanofibers Made of Self-Assembled Peptides to Become Multifunctional Stimuli-Sensitive Nanovectors of Anticancer Drug Doxorubicin

Self-assembled peptides possess remarkable potential as targeted drug delivery systems and key applications dwell anti-cancer therapy. Peptides can self-assemble into nanostructures of diverse sizes and shapes in response to changing environmental conditions (pH, temperature, ionic strength). Herein...

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Main Authors: Valentina Del Genio, Annarita Falanga, Emilie Allard-Vannier, Katel Hervé-Aubert, Marilisa Leone, Rosa Bellavita, Rustem Uzbekov, Igor Chourpa, Stefania Galdiero
Format: Article
Language:English
Published: MDPI AG 2022-07-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/14/8/1544
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author Valentina Del Genio
Annarita Falanga
Emilie Allard-Vannier
Katel Hervé-Aubert
Marilisa Leone
Rosa Bellavita
Rustem Uzbekov
Igor Chourpa
Stefania Galdiero
author_facet Valentina Del Genio
Annarita Falanga
Emilie Allard-Vannier
Katel Hervé-Aubert
Marilisa Leone
Rosa Bellavita
Rustem Uzbekov
Igor Chourpa
Stefania Galdiero
author_sort Valentina Del Genio
collection DOAJ
description Self-assembled peptides possess remarkable potential as targeted drug delivery systems and key applications dwell anti-cancer therapy. Peptides can self-assemble into nanostructures of diverse sizes and shapes in response to changing environmental conditions (pH, temperature, ionic strength). Herein, we investigated the development of self-assembled peptide-based nanofibers (NFs) with the inclusion of a cell-penetrating peptide (namely gH625) and a matrix metalloproteinase-9 (MMP-9) responsive sequence, which proved to enhance respectively the penetration and tumor-triggered cleavage to release Doxorubicin in Triple Negative Breast Cancer cells where MMP-9 levels are elevated. The NFs formulation has been optimized via critical micelle concentration measurements, fluorescence, and circular dichroism. The final nanovectors were characterized for morphology (TEM), size (hydrodynamic diameter), and surface charge (zeta potential). The Doxo loading and release kinetics were studied in situ, by optical microspectroscopy (fluorescence and surface-enhanced Raman scattering–SERS). Confocal spectral imaging of the Doxo fluorescence was used to study the TNBC models in vitro, in cells with various MMP-9 levels, the drug delivery to cells as well as the resulting cytotoxicity profiles. The results confirm that these NFs are a promising platform to develop novel nanovectors of Doxo, namely in the framework of TNBC treatment.
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spelling doaj.art-5dc81f3f744b4c82942bc1d4b53f31842023-11-30T22:10:53ZengMDPI AGPharmaceutics1999-49232022-07-01148154410.3390/pharmaceutics14081544Design and Validation of Nanofibers Made of Self-Assembled Peptides to Become Multifunctional Stimuli-Sensitive Nanovectors of Anticancer Drug DoxorubicinValentina Del Genio0Annarita Falanga1Emilie Allard-Vannier2Katel Hervé-Aubert3Marilisa Leone4Rosa Bellavita5Rustem Uzbekov6Igor Chourpa7Stefania Galdiero8Department of Pharmacy, School of Medicine, University of Naples ‘Federico II’, Via Domenico Montesano 49, 80131 Naples, ItalyDepartment of Agricultural Science, University of Naples ‘Federico II’, Via Università 100, 80055 Portici, ItalyEA 6295 Nanomédicaments et Nanosondes, Faculté de Pharmacie, Université de Tours, 31 Avenue Monge, 37200 Tours, FranceEA 6295 Nanomédicaments et Nanosondes, Faculté de Pharmacie, Université de Tours, 31 Avenue Monge, 37200 Tours, FranceInstitute of Biostructures and Bioimaging-CNR, 80145 Naples, ItalyDepartment of Pharmacy, School of Medicine, University of Naples ‘Federico II’, Via Domenico Montesano 49, 80131 Naples, ItalyPlateforme Scientifique et Technique “Analyse des Systèmes Biologiques” (PST ASB), UFR de Médecine, 37032 Tours, FranceEA 6295 Nanomédicaments et Nanosondes, Faculté de Pharmacie, Université de Tours, 31 Avenue Monge, 37200 Tours, FranceDepartment of Pharmacy, School of Medicine, University of Naples ‘Federico II’, Via Domenico Montesano 49, 80131 Naples, ItalySelf-assembled peptides possess remarkable potential as targeted drug delivery systems and key applications dwell anti-cancer therapy. Peptides can self-assemble into nanostructures of diverse sizes and shapes in response to changing environmental conditions (pH, temperature, ionic strength). Herein, we investigated the development of self-assembled peptide-based nanofibers (NFs) with the inclusion of a cell-penetrating peptide (namely gH625) and a matrix metalloproteinase-9 (MMP-9) responsive sequence, which proved to enhance respectively the penetration and tumor-triggered cleavage to release Doxorubicin in Triple Negative Breast Cancer cells where MMP-9 levels are elevated. The NFs formulation has been optimized via critical micelle concentration measurements, fluorescence, and circular dichroism. The final nanovectors were characterized for morphology (TEM), size (hydrodynamic diameter), and surface charge (zeta potential). The Doxo loading and release kinetics were studied in situ, by optical microspectroscopy (fluorescence and surface-enhanced Raman scattering–SERS). Confocal spectral imaging of the Doxo fluorescence was used to study the TNBC models in vitro, in cells with various MMP-9 levels, the drug delivery to cells as well as the resulting cytotoxicity profiles. The results confirm that these NFs are a promising platform to develop novel nanovectors of Doxo, namely in the framework of TNBC treatment.https://www.mdpi.com/1999-4923/14/8/1544self-assembling peptidesmagnetic nanoparticlescell-penetrating peptidestriple negative breast cancer
spellingShingle Valentina Del Genio
Annarita Falanga
Emilie Allard-Vannier
Katel Hervé-Aubert
Marilisa Leone
Rosa Bellavita
Rustem Uzbekov
Igor Chourpa
Stefania Galdiero
Design and Validation of Nanofibers Made of Self-Assembled Peptides to Become Multifunctional Stimuli-Sensitive Nanovectors of Anticancer Drug Doxorubicin
Pharmaceutics
self-assembling peptides
magnetic nanoparticles
cell-penetrating peptides
triple negative breast cancer
title Design and Validation of Nanofibers Made of Self-Assembled Peptides to Become Multifunctional Stimuli-Sensitive Nanovectors of Anticancer Drug Doxorubicin
title_full Design and Validation of Nanofibers Made of Self-Assembled Peptides to Become Multifunctional Stimuli-Sensitive Nanovectors of Anticancer Drug Doxorubicin
title_fullStr Design and Validation of Nanofibers Made of Self-Assembled Peptides to Become Multifunctional Stimuli-Sensitive Nanovectors of Anticancer Drug Doxorubicin
title_full_unstemmed Design and Validation of Nanofibers Made of Self-Assembled Peptides to Become Multifunctional Stimuli-Sensitive Nanovectors of Anticancer Drug Doxorubicin
title_short Design and Validation of Nanofibers Made of Self-Assembled Peptides to Become Multifunctional Stimuli-Sensitive Nanovectors of Anticancer Drug Doxorubicin
title_sort design and validation of nanofibers made of self assembled peptides to become multifunctional stimuli sensitive nanovectors of anticancer drug doxorubicin
topic self-assembling peptides
magnetic nanoparticles
cell-penetrating peptides
triple negative breast cancer
url https://www.mdpi.com/1999-4923/14/8/1544
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