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Cellular Analysis and Chemotherapeutic Potential of a Bi-Functionalized Halloysite Nanotube

The surface of halloysite nanotubes (HNTs) was bifunctionalized with two ligands—folic acid and a fluorochrome. In tandem, this combination should selectively target cancer cells and provide a means for imaging the nanoparticle. Modified bi-functionalized HNTs (bi-HNTs) were then doped with the anti...

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Autores principales: Luo, Yangyang, Humayun, Ahmed, Murray, Teresa A., Kemp, Benjamin S., McFarland, Antwine, Liu, Xuan, Mills, David K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650711/
https://www.ncbi.nlm.nih.gov/pubmed/33066206
http://dx.doi.org/10.3390/pharmaceutics12100962
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author Luo, Yangyang
Humayun, Ahmed
Murray, Teresa A.
Kemp, Benjamin S.
McFarland, Antwine
Liu, Xuan
Mills, David K.
author_facet Luo, Yangyang
Humayun, Ahmed
Murray, Teresa A.
Kemp, Benjamin S.
McFarland, Antwine
Liu, Xuan
Mills, David K.
author_sort Luo, Yangyang
collection PubMed
description The surface of halloysite nanotubes (HNTs) was bifunctionalized with two ligands—folic acid and a fluorochrome. In tandem, this combination should selectively target cancer cells and provide a means for imaging the nanoparticle. Modified bi-functionalized HNTs (bi-HNTs) were then doped with the anti-cancer drug methotrexate. bi-HNTs were characterized and subjected to in vitro tests to assess cellular growth and changes in cellular behavior in three cell lines—colon cancer, osteosarcoma, and a pre-osteoblast cell line (MC3T3-E1). Cell viability, proliferation, and cell uptake efficiency were assessed. The bi-HNTs showed cytocompatibility at a wide range of concentrations. Compared with regular-sized HNTs, reduced HNTs (~6 microns) were taken up by cells in more significant amounts, but increased cytotoxicity lead to apoptosis. Multi-photon images confirmed the intracellular location of bi-HNTs, and the method of cell entry was mainly through caveolae-mediated endocytosis. The bi-HNTs showed a high drug loading efficiency with methotrexate and a prolonged period of release. Most importantly, bi-HNTs were designed as a drug carrier to target cancer cells specifically, and imaging data shows that non-cancerous cells were unaffected after exposure to MTX-doped bi-HNTs. All data provide support for our nanoparticle design as a mechanism to selectively target cancer cells and significantly reduce the side-effects caused by off-targeting of anti-cancer drugs.
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spelling pubmed-76507112020-11-10 Cellular Analysis and Chemotherapeutic Potential of a Bi-Functionalized Halloysite Nanotube Luo, Yangyang Humayun, Ahmed Murray, Teresa A. Kemp, Benjamin S. McFarland, Antwine Liu, Xuan Mills, David K. Pharmaceutics Article The surface of halloysite nanotubes (HNTs) was bifunctionalized with two ligands—folic acid and a fluorochrome. In tandem, this combination should selectively target cancer cells and provide a means for imaging the nanoparticle. Modified bi-functionalized HNTs (bi-HNTs) were then doped with the anti-cancer drug methotrexate. bi-HNTs were characterized and subjected to in vitro tests to assess cellular growth and changes in cellular behavior in three cell lines—colon cancer, osteosarcoma, and a pre-osteoblast cell line (MC3T3-E1). Cell viability, proliferation, and cell uptake efficiency were assessed. The bi-HNTs showed cytocompatibility at a wide range of concentrations. Compared with regular-sized HNTs, reduced HNTs (~6 microns) were taken up by cells in more significant amounts, but increased cytotoxicity lead to apoptosis. Multi-photon images confirmed the intracellular location of bi-HNTs, and the method of cell entry was mainly through caveolae-mediated endocytosis. The bi-HNTs showed a high drug loading efficiency with methotrexate and a prolonged period of release. Most importantly, bi-HNTs were designed as a drug carrier to target cancer cells specifically, and imaging data shows that non-cancerous cells were unaffected after exposure to MTX-doped bi-HNTs. All data provide support for our nanoparticle design as a mechanism to selectively target cancer cells and significantly reduce the side-effects caused by off-targeting of anti-cancer drugs. MDPI 2020-10-13 /pmc/articles/PMC7650711/ /pubmed/33066206 http://dx.doi.org/10.3390/pharmaceutics12100962 Text en © 2020 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
Luo, Yangyang
Humayun, Ahmed
Murray, Teresa A.
Kemp, Benjamin S.
McFarland, Antwine
Liu, Xuan
Mills, David K.
Cellular Analysis and Chemotherapeutic Potential of a Bi-Functionalized Halloysite Nanotube
title Cellular Analysis and Chemotherapeutic Potential of a Bi-Functionalized Halloysite Nanotube
title_full Cellular Analysis and Chemotherapeutic Potential of a Bi-Functionalized Halloysite Nanotube
title_fullStr Cellular Analysis and Chemotherapeutic Potential of a Bi-Functionalized Halloysite Nanotube
title_full_unstemmed Cellular Analysis and Chemotherapeutic Potential of a Bi-Functionalized Halloysite Nanotube
title_short Cellular Analysis and Chemotherapeutic Potential of a Bi-Functionalized Halloysite Nanotube
title_sort cellular analysis and chemotherapeutic potential of a bi-functionalized halloysite nanotube
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650711/
https://www.ncbi.nlm.nih.gov/pubmed/33066206
http://dx.doi.org/10.3390/pharmaceutics12100962
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