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A drug-specific nanocarrier design for efficient anticancer therapy
The drug-loading properties of nanocarriers depend on the chemical structures and properties of their building blocks. Here, we customize telodendrimers (linear-dendritic copolymer) to design a nanocarrier with improved in vivo drug delivery characteristics. We do a virtual screen of a library of sm...
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/PMC4499863/ https://www.ncbi.nlm.nih.gov/pubmed/26158623 http://dx.doi.org/10.1038/ncomms8449 |
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author | Shi, Changying Guo, Dandan Xiao, Kai Wang, Xu Wang, Lili Luo, Juntao |
author_facet | Shi, Changying Guo, Dandan Xiao, Kai Wang, Xu Wang, Lili Luo, Juntao |
author_sort | Shi, Changying |
collection | PubMed |
description | The drug-loading properties of nanocarriers depend on the chemical structures and properties of their building blocks. Here, we customize telodendrimers (linear-dendritic copolymer) to design a nanocarrier with improved in vivo drug delivery characteristics. We do a virtual screen of a library of small molecules to identify the optimal building blocks for precise telodendrimer synthesis using peptide chemistry. With rationally designed telodendrimer architectures, we then optimize the drug binding affinity of a nanocarrier by introducing an optimal drug-binding molecule (DBM) without sacrificing the stability of the nanocarrier. To validate the computational predictions, we synthesize a series of nanocarriers and evaluate systematically for doxorubicin delivery. Rhein-containing nanocarriers have sustained drug release, prolonged circulation, increased tolerated dose, reduced toxicity, effective tumor targeting and superior anticancer effects owing to favourable doxorubicin-binding affinity and improved nanoparticle stability. This study demonstrates the feasibility and versatility of the de novo design of telodendrimer nanocarriers for specific drug molecules, which is a promising approach to transform nanocarrier development for drug delivery. |
format | Online Article Text |
id | pubmed-4499863 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
record_format | MEDLINE/PubMed |
spelling | pubmed-44998632016-01-09 A drug-specific nanocarrier design for efficient anticancer therapy Shi, Changying Guo, Dandan Xiao, Kai Wang, Xu Wang, Lili Luo, Juntao Nat Commun Article The drug-loading properties of nanocarriers depend on the chemical structures and properties of their building blocks. Here, we customize telodendrimers (linear-dendritic copolymer) to design a nanocarrier with improved in vivo drug delivery characteristics. We do a virtual screen of a library of small molecules to identify the optimal building blocks for precise telodendrimer synthesis using peptide chemistry. With rationally designed telodendrimer architectures, we then optimize the drug binding affinity of a nanocarrier by introducing an optimal drug-binding molecule (DBM) without sacrificing the stability of the nanocarrier. To validate the computational predictions, we synthesize a series of nanocarriers and evaluate systematically for doxorubicin delivery. Rhein-containing nanocarriers have sustained drug release, prolonged circulation, increased tolerated dose, reduced toxicity, effective tumor targeting and superior anticancer effects owing to favourable doxorubicin-binding affinity and improved nanoparticle stability. This study demonstrates the feasibility and versatility of the de novo design of telodendrimer nanocarriers for specific drug molecules, which is a promising approach to transform nanocarrier development for drug delivery. 2015-07-09 /pmc/articles/PMC4499863/ /pubmed/26158623 http://dx.doi.org/10.1038/ncomms8449 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 Shi, Changying Guo, Dandan Xiao, Kai Wang, Xu Wang, Lili Luo, Juntao A drug-specific nanocarrier design for efficient anticancer therapy |
title | A drug-specific nanocarrier design for efficient anticancer therapy |
title_full | A drug-specific nanocarrier design for efficient anticancer therapy |
title_fullStr | A drug-specific nanocarrier design for efficient anticancer therapy |
title_full_unstemmed | A drug-specific nanocarrier design for efficient anticancer therapy |
title_short | A drug-specific nanocarrier design for efficient anticancer therapy |
title_sort | drug-specific nanocarrier design for efficient anticancer therapy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4499863/ https://www.ncbi.nlm.nih.gov/pubmed/26158623 http://dx.doi.org/10.1038/ncomms8449 |
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