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Folic Acid-Modified Ibrutinib-Loaded Silk Fibroin Nanoparticles for Cancer Cell Therapy with Over-Expressed Folate Receptor

The anticancer drug ibrutinib (IB), also known as PCI-32765, is a compound that irreversibly inhibits Bruton’s tyrosine kinase (BTK) and was initially developed as a treatment option for B-cell lineage neoplasms. Its action is not limited to B-cells, as it is expressed in all hematopoietic lineages...

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Autores principales: Fuster, Marta G., Montalbán, Mercedes G., Moulefera, Imane, Víllora, Gloria, Kaplan, David L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10146313/
https://www.ncbi.nlm.nih.gov/pubmed/37111671
http://dx.doi.org/10.3390/pharmaceutics15041186
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author Fuster, Marta G.
Montalbán, Mercedes G.
Moulefera, Imane
Víllora, Gloria
Kaplan, David L.
author_facet Fuster, Marta G.
Montalbán, Mercedes G.
Moulefera, Imane
Víllora, Gloria
Kaplan, David L.
author_sort Fuster, Marta G.
collection PubMed
description The anticancer drug ibrutinib (IB), also known as PCI-32765, is a compound that irreversibly inhibits Bruton’s tyrosine kinase (BTK) and was initially developed as a treatment option for B-cell lineage neoplasms. Its action is not limited to B-cells, as it is expressed in all hematopoietic lineages and plays a crucial role in the tumor microenvironment. However, clinical trials with the drug have resulted in conflicting outcomes against solid tumors. In this study, folic acid-conjugated silk nanoparticles were used for the targeted delivery of IB to the cancer cell lines HeLa, BT-474, and SKBR3 by exploiting the overexpression of folate receptors on their surfaces. The results were compared with those of control healthy cells (EA.hy926). Cellular uptake studies confirmed total internalization of the nanoparticles functionalized by this procedure in the cancer cells after 24 h, compared to nanoparticles not functionalized with folic acid, suggesting that cellular uptake was mediated by folate receptors overexpressed in the cancer cells. The results indicate that the developed nanocarrier can be used for drug targeting applications by enhancing IB uptake in cancer cells with folate receptor overexpression.
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spelling pubmed-101463132023-04-29 Folic Acid-Modified Ibrutinib-Loaded Silk Fibroin Nanoparticles for Cancer Cell Therapy with Over-Expressed Folate Receptor Fuster, Marta G. Montalbán, Mercedes G. Moulefera, Imane Víllora, Gloria Kaplan, David L. Pharmaceutics Article The anticancer drug ibrutinib (IB), also known as PCI-32765, is a compound that irreversibly inhibits Bruton’s tyrosine kinase (BTK) and was initially developed as a treatment option for B-cell lineage neoplasms. Its action is not limited to B-cells, as it is expressed in all hematopoietic lineages and plays a crucial role in the tumor microenvironment. However, clinical trials with the drug have resulted in conflicting outcomes against solid tumors. In this study, folic acid-conjugated silk nanoparticles were used for the targeted delivery of IB to the cancer cell lines HeLa, BT-474, and SKBR3 by exploiting the overexpression of folate receptors on their surfaces. The results were compared with those of control healthy cells (EA.hy926). Cellular uptake studies confirmed total internalization of the nanoparticles functionalized by this procedure in the cancer cells after 24 h, compared to nanoparticles not functionalized with folic acid, suggesting that cellular uptake was mediated by folate receptors overexpressed in the cancer cells. The results indicate that the developed nanocarrier can be used for drug targeting applications by enhancing IB uptake in cancer cells with folate receptor overexpression. MDPI 2023-04-07 /pmc/articles/PMC10146313/ /pubmed/37111671 http://dx.doi.org/10.3390/pharmaceutics15041186 Text en © 2023 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
Fuster, Marta G.
Montalbán, Mercedes G.
Moulefera, Imane
Víllora, Gloria
Kaplan, David L.
Folic Acid-Modified Ibrutinib-Loaded Silk Fibroin Nanoparticles for Cancer Cell Therapy with Over-Expressed Folate Receptor
title Folic Acid-Modified Ibrutinib-Loaded Silk Fibroin Nanoparticles for Cancer Cell Therapy with Over-Expressed Folate Receptor
title_full Folic Acid-Modified Ibrutinib-Loaded Silk Fibroin Nanoparticles for Cancer Cell Therapy with Over-Expressed Folate Receptor
title_fullStr Folic Acid-Modified Ibrutinib-Loaded Silk Fibroin Nanoparticles for Cancer Cell Therapy with Over-Expressed Folate Receptor
title_full_unstemmed Folic Acid-Modified Ibrutinib-Loaded Silk Fibroin Nanoparticles for Cancer Cell Therapy with Over-Expressed Folate Receptor
title_short Folic Acid-Modified Ibrutinib-Loaded Silk Fibroin Nanoparticles for Cancer Cell Therapy with Over-Expressed Folate Receptor
title_sort folic acid-modified ibrutinib-loaded silk fibroin nanoparticles for cancer cell therapy with over-expressed folate receptor
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10146313/
https://www.ncbi.nlm.nih.gov/pubmed/37111671
http://dx.doi.org/10.3390/pharmaceutics15041186
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