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...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2022-07-01
|
Series: | Pharmaceutics |
Subjects: | |
Online Access: | https://www.mdpi.com/1999-4923/14/8/1544 |
_version_ | 1827626017029619712 |
---|---|
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. |
first_indexed | 2024-03-09T12:46:46Z |
format | Article |
id | doaj.art-5dc81f3f744b4c82942bc1d4b53f3184 |
institution | Directory Open Access Journal |
issn | 1999-4923 |
language | English |
last_indexed | 2024-03-09T12:46:46Z |
publishDate | 2022-07-01 |
publisher | MDPI AG |
record_format | Article |
series | Pharmaceutics |
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 |
work_keys_str_mv | AT valentinadelgenio designandvalidationofnanofibersmadeofselfassembledpeptidestobecomemultifunctionalstimulisensitivenanovectorsofanticancerdrugdoxorubicin AT annaritafalanga designandvalidationofnanofibersmadeofselfassembledpeptidestobecomemultifunctionalstimulisensitivenanovectorsofanticancerdrugdoxorubicin AT emilieallardvannier designandvalidationofnanofibersmadeofselfassembledpeptidestobecomemultifunctionalstimulisensitivenanovectorsofanticancerdrugdoxorubicin AT katelherveaubert designandvalidationofnanofibersmadeofselfassembledpeptidestobecomemultifunctionalstimulisensitivenanovectorsofanticancerdrugdoxorubicin AT marilisaleone designandvalidationofnanofibersmadeofselfassembledpeptidestobecomemultifunctionalstimulisensitivenanovectorsofanticancerdrugdoxorubicin AT rosabellavita designandvalidationofnanofibersmadeofselfassembledpeptidestobecomemultifunctionalstimulisensitivenanovectorsofanticancerdrugdoxorubicin AT rustemuzbekov designandvalidationofnanofibersmadeofselfassembledpeptidestobecomemultifunctionalstimulisensitivenanovectorsofanticancerdrugdoxorubicin AT igorchourpa designandvalidationofnanofibersmadeofselfassembledpeptidestobecomemultifunctionalstimulisensitivenanovectorsofanticancerdrugdoxorubicin AT stefaniagaldiero designandvalidationofnanofibersmadeofselfassembledpeptidestobecomemultifunctionalstimulisensitivenanovectorsofanticancerdrugdoxorubicin |