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High-molecular weight star conjugates containing docetaxel with high anti-tumor activity and low systemic toxicity in vivo
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SYSNO ASEP 0439488 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název High-molecular weight star conjugates containing docetaxel with high anti-tumor activity and low systemic toxicity in vivo Tvůrce(i) Etrych, Tomáš (UMCH-V) RID, ORCID
Strohalm, Jiří (UMCH-V)
Šírová, Milada (MBU-M) RID, ORCID
Tomalová, Barbora (MBU-M) ORCID
Rossmann, Pavel (MBU-M)
Říhová, Blanka (MBU-M) RID
Ulbrich, Karel (UMCH-V) RID
Kovář, Marek (MBU-M) RID, ORCIDZdroj.dok. Polymer Chemistry . - : Royal Society of Chemistry - ISSN 1759-9954
Roč. 6, č. 1 (2015), s. 160-170Poč.str. 11 s. Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova star polymer ; HPMA copolymers ; docetaxel Vědní obor RIV CD - Makromolekulární chemie Vědní obor RIV – spolupráce Mikrobiologický ústav - Imunologie CEP GAP301/11/0325 GA ČR - Grantová agentura ČR GCP207/12/J030 GA ČR - Grantová agentura ČR EE2.3.20.0055 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Institucionální podpora UMCH-V - RVO:61389013 ; MBU-M - RVO:61388971 UT WOS 000345898100017 EID SCOPUS 84914680188 DOI 10.1039/C4PY01120A Anotace Here we present the polymer conjugates where the core formed by poly(amido amine) dendrimers was grafted with semitelechelic N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers containing docetaxel (DTX) attached by a pH-sensitive hydrazone bond. DTX was derivatized with three different keto acids prior to attachment to the polymer carrier to introduce reactive keto groups into the drug. The therapeutic efficacy of such high-molecular-weight star conjugates is based on: (a) the enhanced permeability and retention (EPR) effect facilitating selective accumulation within solid tumors; (b) pH-controlled release of the drug, thus ensuring faster DTX release in the mildly acidic tumor microenvironment. The star DTX conjugate had a remarkably higher maximum tolerated dose in comparison with free DTX when administered as a single i.v. injection ([similar]160 mg kg−1vs. 40 mg kg−1 of DTX) in C57BL/6 mice. The star DTX conjugate showed significantly higher antitumor activity than free drug in the EL4 T cell lymphoma growing in syngeneic C57BL/6 mice even when given at the same dose (20 mg kg−1 of DTX eq.). Thus, the star DTX conjugates exert a much higher therapeutic activity and yet a lower systemic toxicity than free DTX. Pracoviště Ústav makromolekulární chemie Kontakt Eva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358 Rok sběru 2015
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