Počet záznamů: 1
Superior penetration and cytotoxicity of HPMA copolymer conjugates of pirarubicin in tumor cell spheroid
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SYSNO ASEP 0507279 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Superior penetration and cytotoxicity of HPMA copolymer conjugates of pirarubicin in tumor cell spheroid Tvůrce(i) Nakamura, H. (JP)
Koziolová, Eva (UMCH-V) RID, ORCID
Chytil, Petr (UMCH-V) RID, ORCID
Etrych, Tomáš (UMCH-V) RID, ORCID
Haratake, M. (JP)
Maeda, H. (JP)Zdroj.dok. Molecular Pharmaceutics. - : American Chemical Society - ISSN 1543-8384
Roč. 16, č. 8 (2019), s. 3452-3459Poč.str. 8 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova pirarubicin (THP) ; tumor spheroid cell ; HPMA polymer Vědní obor RIV CD - Makromolekulární chemie Obor OECD Polymer science CEP GA17-13283S GA ČR - Grantová agentura ČR LQ1604 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy NV16-28600A GA MZd - Ministerstvo zdravotnictví Způsob publikování Omezený přístup Institucionální podpora UMCH-V - RVO:61389013 UT WOS 000480371700012 EID SCOPUS 85070856390 DOI 10.1021/acs.molpharmaceut.9b00248 Anotace N-(2-Hydroxypropyl)methacrylamide copolymer conjugates of pirarubicin (THP), P-THP, accumulates selectively in solid tumor tissue by the enhanced permeability and retention (EPR) effect. Despite of high accumulation in solid tumors, some macromolecular antitumor agents show poor therapeutic outcome because of poor tissue diffusion into the tumor as well as obstructed tumor blood flow. Here, we confirmed that cellular uptake of P-THP was 25 times less than that of free THP at 1–4 h incubation time in vitro. The passage of P-THP through the confluent tight-monolayer cells junction was 12 times higher than free THP, and P-THP penetrated deeper into the tumor cell spheroid (1.3–1.7-fold) than free THP in 4 h. In addition, P-THP showed cytotoxicity comparable to that of free THP to tumor-cells in spheroid form, despite of 7 times lower cytotoxicity of P-THP to the monolayer cells to that of free THP in vitro. These results indicate that P-THP administration can exhibit deeper diffusion into the tumor cell spheroid than free THP. As a consequence, P-THP exhibits more efficient antitumor activity than free THP in vivo, which is also supported by better pharmacokinetics and tumor accumulation of P-THP than free THP. Pracoviště Ústav makromolekulární chemie Kontakt Eva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358 Rok sběru 2020 Elektronická adresa https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.9b00248
Počet záznamů: 1