Polymer nitric oxide donors potentiate the treatment of experimental solid tumours by increasing drug accumulation in the tumour tissue
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F18%3A00481666" target="_blank" >RIV/61388971:_____/18:00481666 - isvavai.cz</a>
Alternative codes found
RIV/61389013:_____/18:00481666
Result on the web
<a href="http://dx.doi.org/10.1016/j.jconrel.2017.11.017" target="_blank" >http://dx.doi.org/10.1016/j.jconrel.2017.11.017</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.jconrel.2017.11.017" target="_blank" >10.1016/j.jconrel.2017.11.017</a>
Alternative languages
Result language
angličtina
Original language name
Polymer nitric oxide donors potentiate the treatment of experimental solid tumours by increasing drug accumulation in the tumour tissue
Original language description
The delivery of nitric oxide (NO) specifically to solid tumours was explored in this study as a strategy to augment the passive accumulation of nanomedicines in tumours induced by the Enhanced Permeability and Retention (EPR) effect. An increase in accumulation was achieved by the binding of the chemical precursor of NO, based on an organic nitrate, to a water-soluble synthetic polymer drug carrier. Four structurally different N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymer NO donors were synthesized. Depending on their chemical structure, two of these donors were hydrolytically stable, while two rapidly released the parent nitrate under acidic conditions, mimicking the intracellular environment. The polymer NO donors were shown to overcome the drawbacks related to low-molecular-weight NO releasing compounds, namely systemic toxicity, lack of site specificity, and fast blood clearance. The NO donors showed intracellular NO release upon incubation with tumour cells. In vivo, they potentiated the EPR effect, resulting in an increased accumulation of polymer-bound cytotoxic drug doxorubicin (Dox) in EL4 T-cell lymphoma inoculated in mice. This led to a better therapeutic outcome in the treatment of lymphoma with the high-molecular-weight polymer conjugates carrying Dox but not in the treatment with the free Dox. The localized augmentation of the EPR effect via the tumour-specific NO delivery system can be viewed as a promising strategy to potentiate polymer-based tumour therapy without increasing systemic toxicity.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10606 - Microbiology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
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
Journal of Controlled Release
ISSN
0168-3659
e-ISSN
—
Volume of the periodical
269
Issue of the periodical within the volume
10 January
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
11
Pages from-to
214-224
UT code for WoS article
000423760400019
EID of the result in the Scopus database
2-s2.0-85034437726