Augmentation of the enhanced permeability and retention effect with nitric oxide-generating agents improves the therapeutic effects of nanomedicines

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F18%3A00497718" target="_blank" >RIV/61389013:_____/18:00497718 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1158/1535-7163.MCT-18-0696" target="_blank" >http://dx.doi.org/10.1158/1535-7163.MCT-18-0696</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1158/1535-7163.MCT-18-0696" target="_blank" >10.1158/1535-7163.MCT-18-0696</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Augmentation of the enhanced permeability and retention effect with nitric oxide-generating agents improves the therapeutic effects of nanomedicines

Popis výsledku v původním jazyce

Enhanced permeability and retention (EPR) effect–based nanomedicine is a promising strategy for successful anticancer therapy. The EPR effect is based on tumor blood flow. Because advanced large tumors, as frequently seen in clinical settings, are heterogeneous, with regions of defective vasculature and blood flow, achieving the desired tumor drug delivery is difficult. Here, we utilized the EPR effect to increase drug delivery. To augment the EPR effect for improved therapeutic effects of nanomedicine, we exploited vascular mediators—the nitric oxide (NO) generators nitroglycerin (NG), hydroxyurea, and l-arginine. These compounds generate NO in tumors with relatively high selectivity. Using different nanosized drugs in our protocol significantly increased (1.5–2 times) delivery of nanomedicines to different solid tumor models, along with markedly improving (2–3-fold) the antitumor effects of these drugs. Also, in 7,12-dimethylbenz[a]anthracene–induced advanced end-stage breast cancer, often seen in clinical settings, 2 mg/kg polymer-conjugated pirarubicin (P-THP) with NG (0.2 mg/mouse) showed better effects than did 5 mg/kg P-THP, and 5 mg/kg P-THP used with NG resulted in cures or stable tumors (no tumor growth) for up to 120 days. Moreover, in a murine autochthonous azoxymethane/dextran sulfate sodium-induced colon cancer model, NO donors markedly improved the therapeutic effects of P-THP even after just one injection, results that were comparable with those achieved with three weekly P-THP treatments. These findings strongly suggest the potential usefulness of NO donors as EPR effect enhancers to improve the therapeutic efficacy of nanomedicines.

Název v anglickém jazyce

Augmentation of the enhanced permeability and retention effect with nitric oxide-generating agents improves the therapeutic effects of nanomedicines

Popis výsledku anglicky

Enhanced permeability and retention (EPR) effect–based nanomedicine is a promising strategy for successful anticancer therapy. The EPR effect is based on tumor blood flow. Because advanced large tumors, as frequently seen in clinical settings, are heterogeneous, with regions of defective vasculature and blood flow, achieving the desired tumor drug delivery is difficult. Here, we utilized the EPR effect to increase drug delivery. To augment the EPR effect for improved therapeutic effects of nanomedicine, we exploited vascular mediators—the nitric oxide (NO) generators nitroglycerin (NG), hydroxyurea, and l-arginine. These compounds generate NO in tumors with relatively high selectivity. Using different nanosized drugs in our protocol significantly increased (1.5–2 times) delivery of nanomedicines to different solid tumor models, along with markedly improving (2–3-fold) the antitumor effects of these drugs. Also, in 7,12-dimethylbenz[a]anthracene–induced advanced end-stage breast cancer, often seen in clinical settings, 2 mg/kg polymer-conjugated pirarubicin (P-THP) with NG (0.2 mg/mouse) showed better effects than did 5 mg/kg P-THP, and 5 mg/kg P-THP used with NG resulted in cures or stable tumors (no tumor growth) for up to 120 days. Moreover, in a murine autochthonous azoxymethane/dextran sulfate sodium-induced colon cancer model, NO donors markedly improved the therapeutic effects of P-THP even after just one injection, results that were comparable with those achieved with three weekly P-THP treatments. These findings strongly suggest the potential usefulness of NO donors as EPR effect enhancers to improve the therapeutic efficacy of nanomedicines.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10404 - Polymer science

Projekt

<a href="/cs/project/NV16-28594A" target="_blank" >NV16-28594A: Pokročilá metoda fluorescenčně naváděné endoskopické chirurgie</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

Molecular Cancer Therapeutics

ISSN

1535-7163

e-ISSN

—

Svazek periodika

17

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

11

Strana od-do

2643-2653

Kód UT WoS článku

000452377000014

EID výsledku v databázi Scopus

2-s2.0-85057609707