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Effects of hypoxia and nanocarrier size on pH-responsive nano-delivery system to solid tumors
One of the special features of solid tumors is the acidity of the tumor microenvironment, which is mainly due to the presence of hypoxic regions. Therefore, pH-responsive drug delivery systems have recently been highly welcomed. In the present study, a comprehensive mathematical model is presented b...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481507/ https://www.ncbi.nlm.nih.gov/pubmed/34588504 http://dx.doi.org/10.1038/s41598-021-98638-w |
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author | Soltani, M. Souri, Mohammad Moradi Kashkooli, Farshad |
author_facet | Soltani, M. Souri, Mohammad Moradi Kashkooli, Farshad |
author_sort | Soltani, M. |
collection | PubMed |
description | One of the special features of solid tumors is the acidity of the tumor microenvironment, which is mainly due to the presence of hypoxic regions. Therefore, pH-responsive drug delivery systems have recently been highly welcomed. In the present study, a comprehensive mathematical model is presented based on extravascular drug release paradigm. Accordingly, drug delivery system using pH-responsive nanocarriers is taken into account to examine the impacts of hypoxic regions as well as the size of nanocarriers for cancerous cell-death. The extent of hypoxic regions is controlled by vascular density. This means that regions with very low vascular density represent regions of hypoxia. Using this mathematical model, it is possible to simulate the extracellular and intracellular concentrations of drug by considering the association/disassociation of the free drug to the cell-surface receptors and cellular uptake. Results show that nanocarriers with smaller sizes are more effective due to higher accumulation in the tumor tissue interstitium. The small size of the nanocarriers also allows them to penetrate deeper, so they can expose a larger portion of the tumor to the drug. Additionally, the presence of hypoxic regions in tumor reduces the fraction of killed cancer cells due to reduced penetration depth. The proposed model can be considered for optimizing and developing pH-sensitive delivery systems to reduce both cost and time of the process. |
format | Online Article Text |
id | pubmed-8481507 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-84815072021-10-01 Effects of hypoxia and nanocarrier size on pH-responsive nano-delivery system to solid tumors Soltani, M. Souri, Mohammad Moradi Kashkooli, Farshad Sci Rep Article One of the special features of solid tumors is the acidity of the tumor microenvironment, which is mainly due to the presence of hypoxic regions. Therefore, pH-responsive drug delivery systems have recently been highly welcomed. In the present study, a comprehensive mathematical model is presented based on extravascular drug release paradigm. Accordingly, drug delivery system using pH-responsive nanocarriers is taken into account to examine the impacts of hypoxic regions as well as the size of nanocarriers for cancerous cell-death. The extent of hypoxic regions is controlled by vascular density. This means that regions with very low vascular density represent regions of hypoxia. Using this mathematical model, it is possible to simulate the extracellular and intracellular concentrations of drug by considering the association/disassociation of the free drug to the cell-surface receptors and cellular uptake. Results show that nanocarriers with smaller sizes are more effective due to higher accumulation in the tumor tissue interstitium. The small size of the nanocarriers also allows them to penetrate deeper, so they can expose a larger portion of the tumor to the drug. Additionally, the presence of hypoxic regions in tumor reduces the fraction of killed cancer cells due to reduced penetration depth. The proposed model can be considered for optimizing and developing pH-sensitive delivery systems to reduce both cost and time of the process. Nature Publishing Group UK 2021-09-29 /pmc/articles/PMC8481507/ /pubmed/34588504 http://dx.doi.org/10.1038/s41598-021-98638-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Soltani, M. Souri, Mohammad Moradi Kashkooli, Farshad Effects of hypoxia and nanocarrier size on pH-responsive nano-delivery system to solid tumors |
title | Effects of hypoxia and nanocarrier size on pH-responsive nano-delivery system to solid tumors |
title_full | Effects of hypoxia and nanocarrier size on pH-responsive nano-delivery system to solid tumors |
title_fullStr | Effects of hypoxia and nanocarrier size on pH-responsive nano-delivery system to solid tumors |
title_full_unstemmed | Effects of hypoxia and nanocarrier size on pH-responsive nano-delivery system to solid tumors |
title_short | Effects of hypoxia and nanocarrier size on pH-responsive nano-delivery system to solid tumors |
title_sort | effects of hypoxia and nanocarrier size on ph-responsive nano-delivery system to solid tumors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481507/ https://www.ncbi.nlm.nih.gov/pubmed/34588504 http://dx.doi.org/10.1038/s41598-021-98638-w |
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