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Polymer nitric oxide donors potentiate the treatment of experimental solid tumours by increasing drug accumulation in the tumour tissue
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SYSNO ASEP 0481666 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Polymer nitric oxide donors potentiate the treatment of experimental solid tumours by increasing drug accumulation in the tumour tissue Tvůrce(i) Studenovský, Martin (UMCH-V) RID, ORCID
Sivák, Ladislav (MBU-M) RID
Sedláček, Ondřej (UMCH-V) RID, ORCID
Konefal, Rafal (UMCH-V) RID, ORCID
Horková, Veronika (MBU-M)
Etrych, Tomáš (UMCH-V) RID, ORCID
Kovář, Marek (MBU-M) RID, ORCID
Říhová, Blanka (MBU-M) RID
Šírová, Milada (MBU-M) RID, ORCIDZdroj.dok. Journal of Controlled Release. - : Elsevier - ISSN 0168-3659
Roč. 269, 10 January (2018), s. 214-224Poč.str. 11 s. Jazyk dok. eng - angličtina Země vyd. NL - Nizozemsko Klíč. slova enhanced permeability and retention effect ; nitric oxide donor ; polymer-based cytotoxic drugs Vědní obor RIV CD - Makromolekulární chemie Obor OECD Polymer science Vědní obor RIV – spolupráce Mikrobiologický ústav - Mikrobiologie, virologie CEP GA14-12742S GA ČR - Grantová agentura ČR NV16-28600A GA MZd - Ministerstvo zdravotnictví LQ1604 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy ED1.1.00/02.0109 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Institucionální podpora UMCH-V - RVO:61389013 ; MBU-M - RVO:61388971 UT WOS 000423760400019 EID SCOPUS 85034437726 DOI 10.1016/j.jconrel.2017.11.017 Anotace 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. Pracoviště Ústav makromolekulární chemie Kontakt Eva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358 Rok sběru 2019
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