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A Paclitaxel-Loaded Recombinant Polypeptide Nanoparticle Outperforms Abraxane in Multiple Murine Cancer Models
Packaging clinically relevant hydrophobic drugs into a self-assembled nanoparticle can improve their aqueous solubility, plasma half-life, tumor specific uptake and therapeutic potential. To this end, here we conjugated paclitaxel (PTX) to recombinant chimeric polypeptides (CPs) that spontaneously s...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4753781/ https://www.ncbi.nlm.nih.gov/pubmed/26239362 http://dx.doi.org/10.1038/ncomms8939 |
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author | Bhattacharyya, Jayanta Bellucci, Joseph J. Weitzhandler, Isaac McDaniel, Jonathan R. Spasojevic, Ivan Li, Xinghai Lin, Chao-Chieh Chi, Jen-Tsan Ashley Chilkoti, Ashutosh |
author_facet | Bhattacharyya, Jayanta Bellucci, Joseph J. Weitzhandler, Isaac McDaniel, Jonathan R. Spasojevic, Ivan Li, Xinghai Lin, Chao-Chieh Chi, Jen-Tsan Ashley Chilkoti, Ashutosh |
author_sort | Bhattacharyya, Jayanta |
collection | PubMed |
description | Packaging clinically relevant hydrophobic drugs into a self-assembled nanoparticle can improve their aqueous solubility, plasma half-life, tumor specific uptake and therapeutic potential. To this end, here we conjugated paclitaxel (PTX) to recombinant chimeric polypeptides (CPs) that spontaneously self-assemble into ~60-nm diameter near-monodisperse nanoparticles that increased the systemic exposure of PTX by 7-fold compared to free drug and 2-fold compared to the FDA approved taxane nanoformulation (Abraxane®). The tumor uptake of the CP-PTX nanoparticle was 5-fold greater than free drug and 2-fold greater than Abraxane. In a murine cancer model of human triple negative breast cancer and prostate cancer, CP-PTX induced near complete tumor regression after a single dose in both tumor models, whereas at the same dose, no mice treated with Abraxane survived for more than 80 days (breast) and 60 days (prostate) respectively. These results show that a molecularly engineered nanoparticle with precisely engineered design features outperforms Abraxane, the current gold standard for paclitaxel delivery. |
format | Online Article Text |
id | pubmed-4753781 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
record_format | MEDLINE/PubMed |
spelling | pubmed-47537812016-02-15 A Paclitaxel-Loaded Recombinant Polypeptide Nanoparticle Outperforms Abraxane in Multiple Murine Cancer Models Bhattacharyya, Jayanta Bellucci, Joseph J. Weitzhandler, Isaac McDaniel, Jonathan R. Spasojevic, Ivan Li, Xinghai Lin, Chao-Chieh Chi, Jen-Tsan Ashley Chilkoti, Ashutosh Nat Commun Article Packaging clinically relevant hydrophobic drugs into a self-assembled nanoparticle can improve their aqueous solubility, plasma half-life, tumor specific uptake and therapeutic potential. To this end, here we conjugated paclitaxel (PTX) to recombinant chimeric polypeptides (CPs) that spontaneously self-assemble into ~60-nm diameter near-monodisperse nanoparticles that increased the systemic exposure of PTX by 7-fold compared to free drug and 2-fold compared to the FDA approved taxane nanoformulation (Abraxane®). The tumor uptake of the CP-PTX nanoparticle was 5-fold greater than free drug and 2-fold greater than Abraxane. In a murine cancer model of human triple negative breast cancer and prostate cancer, CP-PTX induced near complete tumor regression after a single dose in both tumor models, whereas at the same dose, no mice treated with Abraxane survived for more than 80 days (breast) and 60 days (prostate) respectively. These results show that a molecularly engineered nanoparticle with precisely engineered design features outperforms Abraxane, the current gold standard for paclitaxel delivery. 2015-08-04 /pmc/articles/PMC4753781/ /pubmed/26239362 http://dx.doi.org/10.1038/ncomms8939 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Bhattacharyya, Jayanta Bellucci, Joseph J. Weitzhandler, Isaac McDaniel, Jonathan R. Spasojevic, Ivan Li, Xinghai Lin, Chao-Chieh Chi, Jen-Tsan Ashley Chilkoti, Ashutosh A Paclitaxel-Loaded Recombinant Polypeptide Nanoparticle Outperforms Abraxane in Multiple Murine Cancer Models |
title | A Paclitaxel-Loaded Recombinant Polypeptide Nanoparticle Outperforms Abraxane in Multiple Murine Cancer Models |
title_full | A Paclitaxel-Loaded Recombinant Polypeptide Nanoparticle Outperforms Abraxane in Multiple Murine Cancer Models |
title_fullStr | A Paclitaxel-Loaded Recombinant Polypeptide Nanoparticle Outperforms Abraxane in Multiple Murine Cancer Models |
title_full_unstemmed | A Paclitaxel-Loaded Recombinant Polypeptide Nanoparticle Outperforms Abraxane in Multiple Murine Cancer Models |
title_short | A Paclitaxel-Loaded Recombinant Polypeptide Nanoparticle Outperforms Abraxane in Multiple Murine Cancer Models |
title_sort | paclitaxel-loaded recombinant polypeptide nanoparticle outperforms abraxane in multiple murine cancer models |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4753781/ https://www.ncbi.nlm.nih.gov/pubmed/26239362 http://dx.doi.org/10.1038/ncomms8939 |
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