Augmentation of the enhanced permeability and retention effect with nitric oxide-generating agents improves the therapeutic effects of nanomedicines
The result's identifiers
Result code in 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>
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
Augmentation of the enhanced permeability and retention effect with nitric oxide-generating agents improves the therapeutic effects of nanomedicines
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10404 - Polymer science
Result continuities
Project
<a href="/en/project/NV16-28594A" target="_blank" >NV16-28594A: Advanced method for fluorescence-guided endoscopic surgery</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Molecular Cancer Therapeutics
ISSN
1535-7163
e-ISSN
—
Volume of the periodical
17
Issue of the periodical within the volume
12
Country of publishing house
US - UNITED STATES
Number of pages
11
Pages from-to
2643-2653
UT code for WoS article
000452377000014
EID of the result in the Scopus database
2-s2.0-85057609707