Histidine-rich glycoprotein-induced vascular normalization improves EPR-mediated drug targeting to and into tumors

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F18%3A00490447" target="_blank" >RIV/61389013:_____/18:00490447 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.jconrel.2018.05.002" target="_blank" >http://dx.doi.org/10.1016/j.jconrel.2018.05.002</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jconrel.2018.05.002" target="_blank" >10.1016/j.jconrel.2018.05.002</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Histidine-rich glycoprotein-induced vascular normalization improves EPR-mediated drug targeting to and into tumors

Popis výsledku v původním jazyce

Tumors are characterized by leaky blood vessels, and by an abnormal and heterogeneous vascular network. These pathophysiological characteristics contribute to the enhanced permeability and retention (EPR) effect, which is one of the key rationales for developing tumor-targeted drug delivery systems. Vessel abnormality and heterogeneity, however, which typically result from excessive pro-angiogenic signaling, can also hinder efficient drug delivery to and into tumors. Using histidine-rich glycoprotein (HRG) knockout and wild type mice, and HRG-overexpressing and normal t241 fibrosarcoma cells, we evaluated the effect of genetically induced and macrophage-mediated vascular normalization on the tumor accumulation and penetration of 10–20 nm-sized polymeric drug carriers based on poly(N-(2-hydroxypropyl)methacrylamide). Multimodal and multiscale optical imaging was employed to show that normalizing the tumor vasculature improves the accumulation of fluorophore-labeled polymers in tumors, and promotes their penetration out of tumor blood vessels deep into the interstitium.

Název v anglickém jazyce

Histidine-rich glycoprotein-induced vascular normalization improves EPR-mediated drug targeting to and into tumors

Popis výsledku anglicky

Tumors are characterized by leaky blood vessels, and by an abnormal and heterogeneous vascular network. These pathophysiological characteristics contribute to the enhanced permeability and retention (EPR) effect, which is one of the key rationales for developing tumor-targeted drug delivery systems. Vessel abnormality and heterogeneity, however, which typically result from excessive pro-angiogenic signaling, can also hinder efficient drug delivery to and into tumors. Using histidine-rich glycoprotein (HRG) knockout and wild type mice, and HRG-overexpressing and normal t241 fibrosarcoma cells, we evaluated the effect of genetically induced and macrophage-mediated vascular normalization on the tumor accumulation and penetration of 10–20 nm-sized polymeric drug carriers based on poly(N-(2-hydroxypropyl)methacrylamide). Multimodal and multiscale optical imaging was employed to show that normalizing the tumor vasculature improves the accumulation of fluorophore-labeled polymers in tumors, and promotes their penetration out of tumor blood vessels deep into the interstitium.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10404 - Polymer science

Projekt

<a href="/cs/project/GA16-17207S" target="_blank" >GA16-17207S: Polymerní léčiva aktivně směrovaná rekombinantním fragmentem protilátky jako terapeutický nástroj v léčbě GD2 pozitivních nádorů</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

Journal of Controlled Release

ISSN

0168-3659

e-ISSN

—

Svazek periodika

282

Číslo periodika v rámci svazku

28 July

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

10

Strana od-do

25-34

Kód UT WoS článku

000436468400004

EID výsledku v databázi Scopus

2-s2.0-85047219473