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Dendrimeric nanosystem consistently circumvents heterogeneous drug response and resistance in pancreatic cancer
Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer with no efficacious treatment. The application of nanomedicine is expected to bring new hope to PDAC treatment. In this study, we report a novel supramolecular dendrimeric nanosystem carrying the anticancer drug doxorubicin, which demonstrat...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10291567/ https://www.ncbi.nlm.nih.gov/pubmed/37366462 http://dx.doi.org/10.1002/EXP.20210003 |
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author | Liu, Juan Chen, Chao Wei, Tuo Gayet, Odile Loncle, Céline Borge, Laurence Dusetti, Nelson Ma, Xiaowei Marson, Domenico Laurini, Erik Pricl, Sabrina Gu, Zhongwei Iovanna, Juan Peng, Ling Liang, Xing‐Jie |
author_facet | Liu, Juan Chen, Chao Wei, Tuo Gayet, Odile Loncle, Céline Borge, Laurence Dusetti, Nelson Ma, Xiaowei Marson, Domenico Laurini, Erik Pricl, Sabrina Gu, Zhongwei Iovanna, Juan Peng, Ling Liang, Xing‐Jie |
author_sort | Liu, Juan |
collection | PubMed |
description | Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer with no efficacious treatment. The application of nanomedicine is expected to bring new hope to PDAC treatment. In this study, we report a novel supramolecular dendrimeric nanosystem carrying the anticancer drug doxorubicin, which demonstrated potent anticancer activity, markedly overcoming the heterogeneity of drug response and resistance of primary cultured tumor cells derived from PDAC patients. This dendrimer nanodrug was constructed with a fluorinated amphiphilic dendrimer, which self‐assembled into micelles nanostructure and encapsulated doxorubicin with high loading. Because of the fine nanosize, stable formulation and acid‐promoted drug release, this dendrimeric nanosystem effectively accumulated in tumor, with deep penetration in tumor tissue and rapid drug uptake/release profile in cells, ultimately resulting in potent anticancer activity and complete suppression of tumor growth in patient‐derived xenografts. Most importantly, this dendrimer nanodrug generated uniform and effective response when treating 35 primary pancreatic cancer cell lines issued from patient samples as a robust platform for preclinical drug efficacy testing. In addition, this dendrimer nanodrug formulation was devoid of adverse effects and showed excellent tolerability. Given all these uniquely advantageous features, this simple and convenient dendrimer nanodrug holds great promise as a potential candidate to treat the deadly PDAC. |
format | Online Article Text |
id | pubmed-10291567 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-102915672023-06-26 Dendrimeric nanosystem consistently circumvents heterogeneous drug response and resistance in pancreatic cancer Liu, Juan Chen, Chao Wei, Tuo Gayet, Odile Loncle, Céline Borge, Laurence Dusetti, Nelson Ma, Xiaowei Marson, Domenico Laurini, Erik Pricl, Sabrina Gu, Zhongwei Iovanna, Juan Peng, Ling Liang, Xing‐Jie Exploration (Beijing) Research Articles Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer with no efficacious treatment. The application of nanomedicine is expected to bring new hope to PDAC treatment. In this study, we report a novel supramolecular dendrimeric nanosystem carrying the anticancer drug doxorubicin, which demonstrated potent anticancer activity, markedly overcoming the heterogeneity of drug response and resistance of primary cultured tumor cells derived from PDAC patients. This dendrimer nanodrug was constructed with a fluorinated amphiphilic dendrimer, which self‐assembled into micelles nanostructure and encapsulated doxorubicin with high loading. Because of the fine nanosize, stable formulation and acid‐promoted drug release, this dendrimeric nanosystem effectively accumulated in tumor, with deep penetration in tumor tissue and rapid drug uptake/release profile in cells, ultimately resulting in potent anticancer activity and complete suppression of tumor growth in patient‐derived xenografts. Most importantly, this dendrimer nanodrug generated uniform and effective response when treating 35 primary pancreatic cancer cell lines issued from patient samples as a robust platform for preclinical drug efficacy testing. In addition, this dendrimer nanodrug formulation was devoid of adverse effects and showed excellent tolerability. Given all these uniquely advantageous features, this simple and convenient dendrimer nanodrug holds great promise as a potential candidate to treat the deadly PDAC. John Wiley and Sons Inc. 2021-08-27 /pmc/articles/PMC10291567/ /pubmed/37366462 http://dx.doi.org/10.1002/EXP.20210003 Text en © 2021 The Authors. Exploration published by Henan University and John Wiley & Sons Australia, Ltd https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Liu, Juan Chen, Chao Wei, Tuo Gayet, Odile Loncle, Céline Borge, Laurence Dusetti, Nelson Ma, Xiaowei Marson, Domenico Laurini, Erik Pricl, Sabrina Gu, Zhongwei Iovanna, Juan Peng, Ling Liang, Xing‐Jie Dendrimeric nanosystem consistently circumvents heterogeneous drug response and resistance in pancreatic cancer |
title | Dendrimeric nanosystem consistently circumvents heterogeneous drug response and resistance in pancreatic cancer |
title_full | Dendrimeric nanosystem consistently circumvents heterogeneous drug response and resistance in pancreatic cancer |
title_fullStr | Dendrimeric nanosystem consistently circumvents heterogeneous drug response and resistance in pancreatic cancer |
title_full_unstemmed | Dendrimeric nanosystem consistently circumvents heterogeneous drug response and resistance in pancreatic cancer |
title_short | Dendrimeric nanosystem consistently circumvents heterogeneous drug response and resistance in pancreatic cancer |
title_sort | dendrimeric nanosystem consistently circumvents heterogeneous drug response and resistance in pancreatic cancer |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10291567/ https://www.ncbi.nlm.nih.gov/pubmed/37366462 http://dx.doi.org/10.1002/EXP.20210003 |
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