Počet záznamů: 1
Polymer donors of nitric oxide improve the treatment of experimental solid tumours with nanosized polymer therapeutics
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SYSNO ASEP 0482796 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Polymer donors of nitric oxide improve the treatment of experimental solid tumours with nanosized polymer therapeutics Tvůrce(i) Šírová, Milada (MBU-M) RID, ORCID
Horková, Veronika (MBU-M)
Etrych, Tomáš (UMCH-V) RID, ORCID
Chytil, Petr (UMCH-V) RID, ORCID
Říhová, Blanka (MBU-M) RID
Studenovský, Martin (UMCH-V) RID, ORCIDZdroj.dok. Journal of Drug Targeting - ISSN 1061-186X
Roč. 25, 9-10 (2017), s. 796-808Poč.str. 13 s. Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova Drug delivery ; HPMA copolymers ; enhanced EPR effect Vědní obor RIV EE - Mikrobiologie, virologie Obor OECD Microbiology Vědní obor RIV – spolupráce Ústav makromolekulární chemie - Makromolekulární chemie CEP GA14-12742S GA ČR - Grantová agentura ČR NV16-28600A GA MZd - Ministerstvo zdravotnictví Institucionální podpora MBU-M - RVO:61388971 ; UMCH-V - RVO:61389013 UT WOS 000415813900006 EID SCOPUS 85027030147 DOI 10.1080/1061186X.2017.1358724 Anotace Polymer carriers based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers with incorporated organic nitrates as nitric oxide (NO) donors were designed with the aim to localise NO generation in solid tumours, thus highly increasing the enhanced permeability and retention (EPR) effect. The NO donors were coupled to the polymer carrier either through a stable bond or through a hydrolytically degradable, pH sensitive, bond. In vivo, the co-administration of the polymer NO donor and HPMA copolymer-bound cytotoxic drug (doxorubicin, Dox) resulted in an improvement in the treatment of murine EL4 T-cell lymphoma. The polymer NO donors neither potentiated the in vitro toxicity of the cytotoxic drug nor exerted any effect on in vivo model without the EPR effect, such as BCL1 leukaemia. Thus, an increase in passive accumulation of the nanomedicine carrying cytotoxic drug via NO-enhanced EPR effect was the operative mechanism of action. The most significant improvement in the therapy was observed in a combination treatment with such a polymer conjugate of Dox, which is characterised by increased circulation in the blood and efficient accumulation in solid tumours. Notably, the combination treatment enabled the development of an anti-tumour immune response, which was previously demonstrated as an important feature of HPMA-based polymer cytotoxic drugs. Pracoviště Mikrobiologický ústav Kontakt Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Rok sběru 2018
Počet záznamů: 1