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Antibody-targeted paclitaxel loaded nanoparticles for the treatment of CD20(+) B-cell lymphoma

We developed a nano-antibody targeted chemotherapy (nATC) delivery strategy in which tumor specific and clinically relevant antibodies (rituximab, anti-CD20) are non-covalently bound to the albumin scaffold of nab-paclitaxel (ABX). We define the nanoparticle formed when the 2 drugs are bound (AR160)...

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Autores principales: Nevala, Wendy K., Butterfield, John T., Sutor, Shari L., Knauer, Daniel J., Markovic, Svetomir N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5381215/
https://www.ncbi.nlm.nih.gov/pubmed/28378801
http://dx.doi.org/10.1038/srep45682
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author Nevala, Wendy K.
Butterfield, John T.
Sutor, Shari L.
Knauer, Daniel J.
Markovic, Svetomir N.
author_facet Nevala, Wendy K.
Butterfield, John T.
Sutor, Shari L.
Knauer, Daniel J.
Markovic, Svetomir N.
author_sort Nevala, Wendy K.
collection PubMed
description We developed a nano-antibody targeted chemotherapy (nATC) delivery strategy in which tumor specific and clinically relevant antibodies (rituximab, anti-CD20) are non-covalently bound to the albumin scaffold of nab-paclitaxel (ABX). We define the nanoparticle formed when the 2 drugs are bound (AR160). The newly created nATC retains the cytotoxicity of ABX and CD20 affinity of rituximab in vitro. We describe the binding characteristics of the ABX and rituximab in AR160 using peptide mapping/Biacore approach. Flow-based methods, including ImageStream and nanoparticle tracking, were used to characterize the AR160 particles in vitro. A mouse model of human B-cell lymphoma was utilized to test in vivo efficacy of AR160 therapy, which suggested improved tumor targeting (biodistribution) as the most likely mechanism of AR160 therapeutic superiority over ABX or rituximab alone. These data suggest a novel platform for nATC delivery using a slight modification of existing cancer drugs with significantly improved treatment efficacy.
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spelling pubmed-53812152017-04-10 Antibody-targeted paclitaxel loaded nanoparticles for the treatment of CD20(+) B-cell lymphoma Nevala, Wendy K. Butterfield, John T. Sutor, Shari L. Knauer, Daniel J. Markovic, Svetomir N. Sci Rep Article We developed a nano-antibody targeted chemotherapy (nATC) delivery strategy in which tumor specific and clinically relevant antibodies (rituximab, anti-CD20) are non-covalently bound to the albumin scaffold of nab-paclitaxel (ABX). We define the nanoparticle formed when the 2 drugs are bound (AR160). The newly created nATC retains the cytotoxicity of ABX and CD20 affinity of rituximab in vitro. We describe the binding characteristics of the ABX and rituximab in AR160 using peptide mapping/Biacore approach. Flow-based methods, including ImageStream and nanoparticle tracking, were used to characterize the AR160 particles in vitro. A mouse model of human B-cell lymphoma was utilized to test in vivo efficacy of AR160 therapy, which suggested improved tumor targeting (biodistribution) as the most likely mechanism of AR160 therapeutic superiority over ABX or rituximab alone. These data suggest a novel platform for nATC delivery using a slight modification of existing cancer drugs with significantly improved treatment efficacy. Nature Publishing Group 2017-04-05 /pmc/articles/PMC5381215/ /pubmed/28378801 http://dx.doi.org/10.1038/srep45682 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Nevala, Wendy K.
Butterfield, John T.
Sutor, Shari L.
Knauer, Daniel J.
Markovic, Svetomir N.
Antibody-targeted paclitaxel loaded nanoparticles for the treatment of CD20(+) B-cell lymphoma
title Antibody-targeted paclitaxel loaded nanoparticles for the treatment of CD20(+) B-cell lymphoma
title_full Antibody-targeted paclitaxel loaded nanoparticles for the treatment of CD20(+) B-cell lymphoma
title_fullStr Antibody-targeted paclitaxel loaded nanoparticles for the treatment of CD20(+) B-cell lymphoma
title_full_unstemmed Antibody-targeted paclitaxel loaded nanoparticles for the treatment of CD20(+) B-cell lymphoma
title_short Antibody-targeted paclitaxel loaded nanoparticles for the treatment of CD20(+) B-cell lymphoma
title_sort antibody-targeted paclitaxel loaded nanoparticles for the treatment of cd20(+) b-cell lymphoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5381215/
https://www.ncbi.nlm.nih.gov/pubmed/28378801
http://dx.doi.org/10.1038/srep45682
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