Transient mild hyperthermia induces E-selectin mediated localization of mesoporous silicon vectors in solid tumors.

<h4>Background</h4>Hyperthermia treatment has been explored as a strategy to overcome biological barriers that hinder effective drug delivery in solid tumors. Most studies have used mild hyperthermia treatment (MHT) to target the delivery of thermo-sensitive liposomes carriers. Others ha...

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Autores principales: Dickson K Kirui, Juahua Mai, Anna-Lisa Palange, Guoting Qin, Anne L van de Ven, Xuewu Liu, Haifa Shen, Mauro Ferrari
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Publicado: Public Library of Science (PLoS) 2014
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spelling oai:doaj.org-article:1b10fcd602d949799a798f7482e81e6a2021-11-18T08:32:21ZTransient mild hyperthermia induces E-selectin mediated localization of mesoporous silicon vectors in solid tumors.1932-620310.1371/journal.pone.0086489https://doaj.org/article/1b10fcd602d949799a798f7482e81e6a2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24558362/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Hyperthermia treatment has been explored as a strategy to overcome biological barriers that hinder effective drug delivery in solid tumors. Most studies have used mild hyperthermia treatment (MHT) to target the delivery of thermo-sensitive liposomes carriers. Others have studied its application to permeabilize tumor vessels and improve tumor interstitial transport. However, the role of MHT in altering tumor vessel interfacial and adhesion properties and its relationship to improved delivery has not been established. In the present study, we evaluated effects of MHT treatment on tumor vessel flow dynamics and expression of adhesion molecules and assessed enhancement in particle localization using mesoporous silicon vectors (MSVs). We also determined the optimal time window at which maximal accumulation occur.<h4>Results</h4>In this study, using intravital microscopy analyses, we showed that temporal mild hyperthermia (∼1 W/cm(2)) amplified delivery and accumulation of MSVs in orthotopic breast cancer tumors. The number of discoidal MSVs (1000×400 nm) adhering to tumor vasculature increased 6-fold for SUM159 tumors and 3-fold for MCF-7 breast cancer tumors. By flow chamber experiments and Western blotting, we established that a temporal increase in E-selectin expression correlated with enhanced particle accumulation. Furthermore, MHT treatment was shown to increase tumor perfusion in a time-dependent fashion.<h4>Conclusions</h4>Our findings reveal that well-timed mild hyperthermia treatment can transiently elevate tumor transport and alter vascular adhesion properties and thereby provides a means to enhance tumor localization of non-thermally sensitive particles such as MSVs. Such enhancement in accumulation could be leveraged to increase therapeutic efficacy and reduce drug dosing in cancer therapy.Dickson K KiruiJuahua MaiAnna-Lisa PalangeGuoting QinAnne L van de VenXuewu LiuHaifa ShenMauro FerrariPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e86489 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Dickson K Kirui
Juahua Mai
Anna-Lisa Palange
Guoting Qin
Anne L van de Ven
Xuewu Liu
Haifa Shen
Mauro Ferrari
Transient mild hyperthermia induces E-selectin mediated localization of mesoporous silicon vectors in solid tumors.
description <h4>Background</h4>Hyperthermia treatment has been explored as a strategy to overcome biological barriers that hinder effective drug delivery in solid tumors. Most studies have used mild hyperthermia treatment (MHT) to target the delivery of thermo-sensitive liposomes carriers. Others have studied its application to permeabilize tumor vessels and improve tumor interstitial transport. However, the role of MHT in altering tumor vessel interfacial and adhesion properties and its relationship to improved delivery has not been established. In the present study, we evaluated effects of MHT treatment on tumor vessel flow dynamics and expression of adhesion molecules and assessed enhancement in particle localization using mesoporous silicon vectors (MSVs). We also determined the optimal time window at which maximal accumulation occur.<h4>Results</h4>In this study, using intravital microscopy analyses, we showed that temporal mild hyperthermia (∼1 W/cm(2)) amplified delivery and accumulation of MSVs in orthotopic breast cancer tumors. The number of discoidal MSVs (1000×400 nm) adhering to tumor vasculature increased 6-fold for SUM159 tumors and 3-fold for MCF-7 breast cancer tumors. By flow chamber experiments and Western blotting, we established that a temporal increase in E-selectin expression correlated with enhanced particle accumulation. Furthermore, MHT treatment was shown to increase tumor perfusion in a time-dependent fashion.<h4>Conclusions</h4>Our findings reveal that well-timed mild hyperthermia treatment can transiently elevate tumor transport and alter vascular adhesion properties and thereby provides a means to enhance tumor localization of non-thermally sensitive particles such as MSVs. Such enhancement in accumulation could be leveraged to increase therapeutic efficacy and reduce drug dosing in cancer therapy.
format article
author Dickson K Kirui
Juahua Mai
Anna-Lisa Palange
Guoting Qin
Anne L van de Ven
Xuewu Liu
Haifa Shen
Mauro Ferrari
author_facet Dickson K Kirui
Juahua Mai
Anna-Lisa Palange
Guoting Qin
Anne L van de Ven
Xuewu Liu
Haifa Shen
Mauro Ferrari
author_sort Dickson K Kirui
title Transient mild hyperthermia induces E-selectin mediated localization of mesoporous silicon vectors in solid tumors.
title_short Transient mild hyperthermia induces E-selectin mediated localization of mesoporous silicon vectors in solid tumors.
title_full Transient mild hyperthermia induces E-selectin mediated localization of mesoporous silicon vectors in solid tumors.
title_fullStr Transient mild hyperthermia induces E-selectin mediated localization of mesoporous silicon vectors in solid tumors.
title_full_unstemmed Transient mild hyperthermia induces E-selectin mediated localization of mesoporous silicon vectors in solid tumors.
title_sort transient mild hyperthermia induces e-selectin mediated localization of mesoporous silicon vectors in solid tumors.
publisher Public Library of Science (PLoS)
publishDate 2014
url https://doaj.org/article/1b10fcd602d949799a798f7482e81e6a
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