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Bio- and Hemo-Compatible Silk Fibroin PEGylated Nanocarriers for 5-Fluorouracil Chemotherapy in Colorectal Cancer: In Vitro Studies

5-fluorouracil (5-FU) remains the gold standard of treatment for colorectal cancer, but its poor bioavailability and high systemic toxicity highlight the urgent need for the development of novel delivery strategies to increase the efficacy of 5-FU treatment. The present study is aimed to design and...

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Autores principales: Hudiță, Ariana, Radu, Ionuț Cristian, Zaharia, Cătălin, Ion, Andreea Cristina, Ginghină, Octav, Gălățeanu, Bianca, Măruțescu, Luminița, Grama, Florin, Tsatsakis, Aristidis, Gurevich, Leonid, Costache, Marieta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160811/
https://www.ncbi.nlm.nih.gov/pubmed/34069731
http://dx.doi.org/10.3390/pharmaceutics13050755
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author Hudiță, Ariana
Radu, Ionuț Cristian
Zaharia, Cătălin
Ion, Andreea Cristina
Ginghină, Octav
Gălățeanu, Bianca
Măruțescu, Luminița
Grama, Florin
Tsatsakis, Aristidis
Gurevich, Leonid
Costache, Marieta
author_facet Hudiță, Ariana
Radu, Ionuț Cristian
Zaharia, Cătălin
Ion, Andreea Cristina
Ginghină, Octav
Gălățeanu, Bianca
Măruțescu, Luminița
Grama, Florin
Tsatsakis, Aristidis
Gurevich, Leonid
Costache, Marieta
author_sort Hudiță, Ariana
collection PubMed
description 5-fluorouracil (5-FU) remains the gold standard of treatment for colorectal cancer, but its poor bioavailability and high systemic toxicity highlight the urgent need for the development of novel delivery strategies to increase the efficacy of 5-FU treatment. The present study is aimed to design and validate a PEGylated Silk Fibroin Nanocarrier (SF/PEG nanoparticles (NPs)) as an efficient 5-FU delivery system for potential intravenous administration. Using the human adenocarcinoma HT–29 cell line as an in vitro model for colorectal cancer, the cytotoxicity screening of the SF/PEG NPs showed that pristine nanocarriers were highly biocompatible, while the addition of 5-FU triggers a dramatic reduction in tumor cell viability, proliferation potential and mitochondrial integrity as well as a significant increase in nitric oxide production. Despite their high in vitro cytotoxicity, the 5-FU SF/PEG NPs were found hemocompatible as no impact on red blood cells hemolysis or the phagocytic activity of the granulocytes was observed. Exposure of HT–29 tumor cells and blood samples to 5-FU SF/PEG NPs augmented the tumor necrosis factor-α levels. Moreover, 5-FU SF/PEG NPs showed an impact on tumor cell migration and invasive potential as both of these processes were inhibited by the NP treatment.
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spelling pubmed-81608112021-05-29 Bio- and Hemo-Compatible Silk Fibroin PEGylated Nanocarriers for 5-Fluorouracil Chemotherapy in Colorectal Cancer: In Vitro Studies Hudiță, Ariana Radu, Ionuț Cristian Zaharia, Cătălin Ion, Andreea Cristina Ginghină, Octav Gălățeanu, Bianca Măruțescu, Luminița Grama, Florin Tsatsakis, Aristidis Gurevich, Leonid Costache, Marieta Pharmaceutics Article 5-fluorouracil (5-FU) remains the gold standard of treatment for colorectal cancer, but its poor bioavailability and high systemic toxicity highlight the urgent need for the development of novel delivery strategies to increase the efficacy of 5-FU treatment. The present study is aimed to design and validate a PEGylated Silk Fibroin Nanocarrier (SF/PEG nanoparticles (NPs)) as an efficient 5-FU delivery system for potential intravenous administration. Using the human adenocarcinoma HT–29 cell line as an in vitro model for colorectal cancer, the cytotoxicity screening of the SF/PEG NPs showed that pristine nanocarriers were highly biocompatible, while the addition of 5-FU triggers a dramatic reduction in tumor cell viability, proliferation potential and mitochondrial integrity as well as a significant increase in nitric oxide production. Despite their high in vitro cytotoxicity, the 5-FU SF/PEG NPs were found hemocompatible as no impact on red blood cells hemolysis or the phagocytic activity of the granulocytes was observed. Exposure of HT–29 tumor cells and blood samples to 5-FU SF/PEG NPs augmented the tumor necrosis factor-α levels. Moreover, 5-FU SF/PEG NPs showed an impact on tumor cell migration and invasive potential as both of these processes were inhibited by the NP treatment. MDPI 2021-05-19 /pmc/articles/PMC8160811/ /pubmed/34069731 http://dx.doi.org/10.3390/pharmaceutics13050755 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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hudiță, Ariana
Radu, Ionuț Cristian
Zaharia, Cătălin
Ion, Andreea Cristina
Ginghină, Octav
Gălățeanu, Bianca
Măruțescu, Luminița
Grama, Florin
Tsatsakis, Aristidis
Gurevich, Leonid
Costache, Marieta
Bio- and Hemo-Compatible Silk Fibroin PEGylated Nanocarriers for 5-Fluorouracil Chemotherapy in Colorectal Cancer: In Vitro Studies
title Bio- and Hemo-Compatible Silk Fibroin PEGylated Nanocarriers for 5-Fluorouracil Chemotherapy in Colorectal Cancer: In Vitro Studies
title_full Bio- and Hemo-Compatible Silk Fibroin PEGylated Nanocarriers for 5-Fluorouracil Chemotherapy in Colorectal Cancer: In Vitro Studies
title_fullStr Bio- and Hemo-Compatible Silk Fibroin PEGylated Nanocarriers for 5-Fluorouracil Chemotherapy in Colorectal Cancer: In Vitro Studies
title_full_unstemmed Bio- and Hemo-Compatible Silk Fibroin PEGylated Nanocarriers for 5-Fluorouracil Chemotherapy in Colorectal Cancer: In Vitro Studies
title_short Bio- and Hemo-Compatible Silk Fibroin PEGylated Nanocarriers for 5-Fluorouracil Chemotherapy in Colorectal Cancer: In Vitro Studies
title_sort bio- and hemo-compatible silk fibroin pegylated nanocarriers for 5-fluorouracil chemotherapy in colorectal cancer: in vitro studies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160811/
https://www.ncbi.nlm.nih.gov/pubmed/34069731
http://dx.doi.org/10.3390/pharmaceutics13050755
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