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Delivery of Proapoptotic Agents in Glioma Cell Lines by TSPO Ligand–Dextran Nanogels

Translocator protein 18-kDa (TSPO) is a versatile mitochondrial target for molecular imaging and therapy. Moreover, selective TSPO ligands have been widely investigated for diagnostic purposes and explored to target drug delivery systems directed to cancer cells overexpressing TSPO. Indeed, poly(d,l...

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Autores principales: Lopalco, Antonio, Cutrignelli, Annalisa, Denora, Nunzio, Perrone, Mara, Iacobazzi, Rosa Maria, Fanizza, Elisabetta, Lopedota, Angela, Depalo, Nicoletta, de Candia, Modesto, Franco, Massimo, Laquintana, Valentino
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979576/
https://www.ncbi.nlm.nih.gov/pubmed/29641449
http://dx.doi.org/10.3390/ijms19041155
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author Lopalco, Antonio
Cutrignelli, Annalisa
Denora, Nunzio
Perrone, Mara
Iacobazzi, Rosa Maria
Fanizza, Elisabetta
Lopedota, Angela
Depalo, Nicoletta
de Candia, Modesto
Franco, Massimo
Laquintana, Valentino
author_facet Lopalco, Antonio
Cutrignelli, Annalisa
Denora, Nunzio
Perrone, Mara
Iacobazzi, Rosa Maria
Fanizza, Elisabetta
Lopedota, Angela
Depalo, Nicoletta
de Candia, Modesto
Franco, Massimo
Laquintana, Valentino
author_sort Lopalco, Antonio
collection PubMed
description Translocator protein 18-kDa (TSPO) is a versatile mitochondrial target for molecular imaging and therapy. Moreover, selective TSPO ligands have been widely investigated for diagnostic purposes and explored to target drug delivery systems directed to cancer cells overexpressing TSPO. Indeed, poly(d,l-lactic-co-glycolic acid (PLGA) polymers and nanocarriers decorated with TSPO ligands are capable of transporting TSPO ligands inside cancer cells, inducing survival inhibition in cancer cells and producing mitochondrial morphology modification. The aim of this work was to prepare nanogels (NGs) made with TSPO ligand dextran conjugates (TSPO-Dex) that are useful as potential delivery systems of two TSPO ligands as apoptotic agents. Synthesis and complete characterization of TSPO–dextran conjugates, an average molecular weights analysis, TSPO ligand release profiles, thermal behaviour and swelling studies were achieved. NG preparation, characterization and in vitro biological studies were also performed. The release of TSPO ligands released from dextran conjugates at 37 °C occurred in human serum at a faster rate than that detected in phosphate buffer. Cytotoxicity studies demonstrated that NGs produced from TSPO ligand–dextran conjugates induce survival inhibition in rat C6 glioma cell lines. Cellular uptake was also proven by fluorescence microscopy.
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spelling pubmed-59795762018-06-10 Delivery of Proapoptotic Agents in Glioma Cell Lines by TSPO Ligand–Dextran Nanogels Lopalco, Antonio Cutrignelli, Annalisa Denora, Nunzio Perrone, Mara Iacobazzi, Rosa Maria Fanizza, Elisabetta Lopedota, Angela Depalo, Nicoletta de Candia, Modesto Franco, Massimo Laquintana, Valentino Int J Mol Sci Article Translocator protein 18-kDa (TSPO) is a versatile mitochondrial target for molecular imaging and therapy. Moreover, selective TSPO ligands have been widely investigated for diagnostic purposes and explored to target drug delivery systems directed to cancer cells overexpressing TSPO. Indeed, poly(d,l-lactic-co-glycolic acid (PLGA) polymers and nanocarriers decorated with TSPO ligands are capable of transporting TSPO ligands inside cancer cells, inducing survival inhibition in cancer cells and producing mitochondrial morphology modification. The aim of this work was to prepare nanogels (NGs) made with TSPO ligand dextran conjugates (TSPO-Dex) that are useful as potential delivery systems of two TSPO ligands as apoptotic agents. Synthesis and complete characterization of TSPO–dextran conjugates, an average molecular weights analysis, TSPO ligand release profiles, thermal behaviour and swelling studies were achieved. NG preparation, characterization and in vitro biological studies were also performed. The release of TSPO ligands released from dextran conjugates at 37 °C occurred in human serum at a faster rate than that detected in phosphate buffer. Cytotoxicity studies demonstrated that NGs produced from TSPO ligand–dextran conjugates induce survival inhibition in rat C6 glioma cell lines. Cellular uptake was also proven by fluorescence microscopy. MDPI 2018-04-11 /pmc/articles/PMC5979576/ /pubmed/29641449 http://dx.doi.org/10.3390/ijms19041155 Text en © 2018 by the authors. 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/).
spellingShingle Article
Lopalco, Antonio
Cutrignelli, Annalisa
Denora, Nunzio
Perrone, Mara
Iacobazzi, Rosa Maria
Fanizza, Elisabetta
Lopedota, Angela
Depalo, Nicoletta
de Candia, Modesto
Franco, Massimo
Laquintana, Valentino
Delivery of Proapoptotic Agents in Glioma Cell Lines by TSPO Ligand–Dextran Nanogels
title Delivery of Proapoptotic Agents in Glioma Cell Lines by TSPO Ligand–Dextran Nanogels
title_full Delivery of Proapoptotic Agents in Glioma Cell Lines by TSPO Ligand–Dextran Nanogels
title_fullStr Delivery of Proapoptotic Agents in Glioma Cell Lines by TSPO Ligand–Dextran Nanogels
title_full_unstemmed Delivery of Proapoptotic Agents in Glioma Cell Lines by TSPO Ligand–Dextran Nanogels
title_short Delivery of Proapoptotic Agents in Glioma Cell Lines by TSPO Ligand–Dextran Nanogels
title_sort delivery of proapoptotic agents in glioma cell lines by tspo ligand–dextran nanogels
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979576/
https://www.ncbi.nlm.nih.gov/pubmed/29641449
http://dx.doi.org/10.3390/ijms19041155
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