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Selective Priming of Tumor Blood Vessels by Radiation Therapy Enhances Nanodrug Delivery
S. Kunjachan, S. Kotb, R. Pola, M. Pechar, R. Kumar, B. Singh, F. Gremse, R. Taleeli, F. Trichard, V. Motto-Ros, L. Sancey, A. Detappe, S. Yasmin-Karim, A. Protti, I. Shanmugam, T. Ireland, T. Etrych, S. Sridhar, O. Tillement, M. Makrigiorgos,...
Jazyk angličtina Země Velká Británie
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
NV16-28594A
MZ0
CEP - Centrální evidence projektů
Digitální knihovna NLK
Plný text - Článek
NLK
Directory of Open Access Journals
od 2011
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od 2011
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od 2011-12-01
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od 2011
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od 2011
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od 2011-01-01
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od 2011-01-01
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od 2011-01-01
Health & Medicine (ProQuest)
od 2011-01-01
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od 2011
- MeSH
- endoteliální buňky pupečníkové žíly (lidské) metabolismus MeSH
- experimentální nádory * krevní zásobení diagnostické zobrazování farmakoterapie metabolismus MeSH
- kovové nanočástice * chemie terapeutické užití MeSH
- lidé MeSH
- magnetická rezonanční angiografie * MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- optické zobrazování * MeSH
- patologická angiogeneze * diagnostické zobrazování farmakoterapie metabolismus MeSH
- systémy cílené aplikace léků * MeSH
- zlato * chemie farmakokinetika farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Effective drug delivery is restricted by pathophysiological barriers in solid tumors. In human pancreatic adenocarcinoma, poorly-permeable blood vessels limit the intratumoral permeation and penetration of chemo or nanotherapeutic drugs. New and clinically viable strategies are urgently sought to breach the neoplastic barriers that prevent effective drug delivery. Here, we present an original idea to boost drug delivery by selectively knocking down the tumor vascular barrier in a human pancreatic cancer model. Clinical radiation activates the tumor endothelial-targeted gold nanoparticles to induce a physical vascular damage due to the high photoelectric interactions. Active modulation of these tumor neovessels lead to distinct changes in tumor vascular permeability. Noninvasive MRI and fluorescence studies, using a short-circulating nanocarrier with MR-sensitive gadolinium and a long-circulating nanocarrier with fluorescence-sensitive nearinfrared dye, demonstrate more than two-fold increase in nanodrug delivery, post tumor vascular modulation. Functional changes in altered tumor blood vessels and its downstream parameters, particularly, changes in Ktrans (permeability), Kep (flux rate), and Ve (extracellular interstitial volume), reflect changes that relate to augmented drug delivery. The proposed dual-targeted therapy effectively invades the tumor vascular barrier and improve nanodrug delivery in a human pancreatic tumor model and it may also be applied to other nonresectable, intransigent tumors that barely respond to standard drug therapies.
Citace poskytuje Crossref.org
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- $a Kunjachan, Sijumon $u Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, United States. sijumon@gmail.com.
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- $a Effective drug delivery is restricted by pathophysiological barriers in solid tumors. In human pancreatic adenocarcinoma, poorly-permeable blood vessels limit the intratumoral permeation and penetration of chemo or nanotherapeutic drugs. New and clinically viable strategies are urgently sought to breach the neoplastic barriers that prevent effective drug delivery. Here, we present an original idea to boost drug delivery by selectively knocking down the tumor vascular barrier in a human pancreatic cancer model. Clinical radiation activates the tumor endothelial-targeted gold nanoparticles to induce a physical vascular damage due to the high photoelectric interactions. Active modulation of these tumor neovessels lead to distinct changes in tumor vascular permeability. Noninvasive MRI and fluorescence studies, using a short-circulating nanocarrier with MR-sensitive gadolinium and a long-circulating nanocarrier with fluorescence-sensitive nearinfrared dye, demonstrate more than two-fold increase in nanodrug delivery, post tumor vascular modulation. Functional changes in altered tumor blood vessels and its downstream parameters, particularly, changes in Ktrans (permeability), Kep (flux rate), and Ve (extracellular interstitial volume), reflect changes that relate to augmented drug delivery. The proposed dual-targeted therapy effectively invades the tumor vascular barrier and improve nanodrug delivery in a human pancreatic tumor model and it may also be applied to other nonresectable, intransigent tumors that barely respond to standard drug therapies.
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