Selective priming of tumor blood vessels by radiation therapy enhances nanodrug delivery

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F19%3A00510512" target="_blank" >RIV/61389013:_____/19:00510512 - isvavai.cz</a>

Result on the web

<a href="https://www.nature.com/articles/s41598-019-50538-w.pdf" target="_blank" >https://www.nature.com/articles/s41598-019-50538-w.pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41598-019-50538-w" target="_blank" >10.1038/s41598-019-50538-w</a>

Result language

angličtina

Original language name

Selective priming of tumor blood vessels by radiation therapy enhances nanodrug delivery

Original language description

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.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10404 - Polymer science

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Scientific Reports

ISSN

2045-2322

e-ISSN

—

Volume of the periodical

9

Issue of the periodical within the volume

1 November

Country of publishing house

GB - UNITED KINGDOM

Number of pages

14

Pages from-to

1-14

UT code for WoS article

000493716000045

EID of the result in the Scopus database

2-s2.0-85074337400