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Tumor-selective peptide-carrier delivery of Paclitaxel increases in vivo activity of the drug
Taxanes are highly effective chemotherapeutic drugs against proliferating cancer and an established option in the standard treatment of ovarian and breast cancer. However, treatment with paclitaxel is associated with severe side effects, including sensory axonal neuropathy, and its poor solubility i...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667195/ https://www.ncbi.nlm.nih.gov/pubmed/26626158 http://dx.doi.org/10.1038/srep17736 |
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author | Brunetti, Jlenia Pillozzi, Serena Falciani, Chiara Depau, Lorenzo Tenori, Eleonora Scali, Silvia Lozzi, Luisa Pini, Alessandro Arcangeli, Annarosa Menichetti, Stefano Bracci, Luisa |
author_facet | Brunetti, Jlenia Pillozzi, Serena Falciani, Chiara Depau, Lorenzo Tenori, Eleonora Scali, Silvia Lozzi, Luisa Pini, Alessandro Arcangeli, Annarosa Menichetti, Stefano Bracci, Luisa |
author_sort | Brunetti, Jlenia |
collection | PubMed |
description | Taxanes are highly effective chemotherapeutic drugs against proliferating cancer and an established option in the standard treatment of ovarian and breast cancer. However, treatment with paclitaxel is associated with severe side effects, including sensory axonal neuropathy, and its poor solubility in water complicates its formulation. In this paper we report the in vitro and in vivo activity of a new form of paclitaxel, modified for conjugation with a tumor-selective tetrabranched peptide carrier (NT4). NT4 selectively targets tumor cells by binding to membrane sulfated glycosaminoglycans (GAG) and to endocytic receptors, like LRP1 and LRP6, which are established tumor markers. Biological activity of NT4-paclitaxel was tested in vitro on MDA-MB 231 and SKOV-3 cell lines, representing breast and ovarian cancer, respectively, and in vivo in an orthotopic mouse model of human breast cancer. Using in vivo bioluminescence imaging, we found that conjugation of paclitaxel with the NT4 peptide led to increased therapeutic activity of the drug in vivo. NT4-paclitaxel induced tumor regression, whereas treatment with unconjugated paclitaxel only produced a reduction in tumor growth. Moreover, unlike paclitaxel, NT4-paclitaxel is very hydrophilic, which may improve its pharmacokinetic profile and allow the use of less toxic dilution buffers, further decreasing its general chemotherapic toxicity. |
format | Online Article Text |
id | pubmed-4667195 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-46671952015-12-08 Tumor-selective peptide-carrier delivery of Paclitaxel increases in vivo activity of the drug Brunetti, Jlenia Pillozzi, Serena Falciani, Chiara Depau, Lorenzo Tenori, Eleonora Scali, Silvia Lozzi, Luisa Pini, Alessandro Arcangeli, Annarosa Menichetti, Stefano Bracci, Luisa Sci Rep Article Taxanes are highly effective chemotherapeutic drugs against proliferating cancer and an established option in the standard treatment of ovarian and breast cancer. However, treatment with paclitaxel is associated with severe side effects, including sensory axonal neuropathy, and its poor solubility in water complicates its formulation. In this paper we report the in vitro and in vivo activity of a new form of paclitaxel, modified for conjugation with a tumor-selective tetrabranched peptide carrier (NT4). NT4 selectively targets tumor cells by binding to membrane sulfated glycosaminoglycans (GAG) and to endocytic receptors, like LRP1 and LRP6, which are established tumor markers. Biological activity of NT4-paclitaxel was tested in vitro on MDA-MB 231 and SKOV-3 cell lines, representing breast and ovarian cancer, respectively, and in vivo in an orthotopic mouse model of human breast cancer. Using in vivo bioluminescence imaging, we found that conjugation of paclitaxel with the NT4 peptide led to increased therapeutic activity of the drug in vivo. NT4-paclitaxel induced tumor regression, whereas treatment with unconjugated paclitaxel only produced a reduction in tumor growth. Moreover, unlike paclitaxel, NT4-paclitaxel is very hydrophilic, which may improve its pharmacokinetic profile and allow the use of less toxic dilution buffers, further decreasing its general chemotherapic toxicity. Nature Publishing Group 2015-12-02 /pmc/articles/PMC4667195/ /pubmed/26626158 http://dx.doi.org/10.1038/srep17736 Text en Copyright © 2015, Macmillan Publishers Limited 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 Brunetti, Jlenia Pillozzi, Serena Falciani, Chiara Depau, Lorenzo Tenori, Eleonora Scali, Silvia Lozzi, Luisa Pini, Alessandro Arcangeli, Annarosa Menichetti, Stefano Bracci, Luisa Tumor-selective peptide-carrier delivery of Paclitaxel increases in vivo activity of the drug |
title | Tumor-selective peptide-carrier delivery of Paclitaxel increases in vivo activity of the drug |
title_full | Tumor-selective peptide-carrier delivery of Paclitaxel increases in vivo activity of the drug |
title_fullStr | Tumor-selective peptide-carrier delivery of Paclitaxel increases in vivo activity of the drug |
title_full_unstemmed | Tumor-selective peptide-carrier delivery of Paclitaxel increases in vivo activity of the drug |
title_short | Tumor-selective peptide-carrier delivery of Paclitaxel increases in vivo activity of the drug |
title_sort | tumor-selective peptide-carrier delivery of paclitaxel increases in vivo activity of the drug |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667195/ https://www.ncbi.nlm.nih.gov/pubmed/26626158 http://dx.doi.org/10.1038/srep17736 |
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