Effects of hypoxia and nanocarrier size on pH-responsive nano-delivery system to solid tumors

Abstract 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 pr...

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Autores principales:	M. Soltani, Mohammad Souri, Farshad Moradi Kashkooli
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/af98c8947e184468bc578d148b1c6635
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spelling	oai:doaj.org-article:af98c8947e184468bc578d148b1c66352021-12-02T18:51:07ZEffects of hypoxia and nanocarrier size on pH-responsive nano-delivery system to solid tumors10.1038/s41598-021-98638-w2045-2322https://doaj.org/article/af98c8947e184468bc578d148b1c66352021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98638-whttps://doaj.org/toc/2045-2322Abstract 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.M. SoltaniMohammad SouriFarshad Moradi KashkooliNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q M. Soltani Mohammad Souri Farshad Moradi Kashkooli Effects of hypoxia and nanocarrier size on pH-responsive nano-delivery system to solid tumors
description	Abstract 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	article
author	M. Soltani Mohammad Souri Farshad Moradi Kashkooli
author_facet	M. Soltani Mohammad Souri Farshad Moradi Kashkooli
author_sort	M. Soltani
title	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_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_sort	effects of hypoxia and nanocarrier size on ph-responsive nano-delivery system to solid tumors
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/af98c8947e184468bc578d148b1c6635
work_keys_str_mv	AT msoltani effectsofhypoxiaandnanocarriersizeonphresponsivenanodeliverysystemtosolidtumors AT mohammadsouri effectsofhypoxiaandnanocarriersizeonphresponsivenanodeliverysystemtosolidtumors AT farshadmoradikashkooli effectsofhypoxiaandnanocarriersizeonphresponsivenanodeliverysystemtosolidtumors
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Effects of hypoxia and nanocarrier size on pH-responsive nano-delivery system to solid tumors

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