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Adaptable polymerization platform for therapeutics with tunable biodegradability
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SYSNO ASEP 0576932 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Adaptable polymerization platform for therapeutics with tunable biodegradability Tvůrce(i) Hrochová, Michaela (UMCH-V)
Kotrchová, Lenka (UMCH-V) RID, ORCID
Frejková, Markéta (UMCH-V) RID, ORCID
Konefal, Rafal (UMCH-V) RID, ORCID
Gao, S. (JP)
Fang, J. (JP)
Kostka, Libor (UMCH-V) RID, ORCID
Etrych, Tomáš (UMCH-V) RID, ORCIDZdroj.dok. Acta Biomaterialia. - : Elsevier - ISSN 1742-7061
Roč. 171, November (2023), s. 417-427Poč.str. 11 s. Jazyk dok. eng - angličtina Země vyd. NL - Nizozemsko Klíč. slova HPMA ; RAFT polymerization ; drug delivery Vědní obor RIV CD - Makromolekulární chemie Obor OECD Polymer science CEP NU21-03-00273 GA MZd - Ministerstvo zdravotnictví LX22NPO5102 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Způsob publikování Open access Institucionální podpora UMCH-V - RVO:61389013 UT WOS 001092764300001 EID SCOPUS 85171286088 DOI 10.1016/j.actbio.2023.09.004 Anotace Biodegradable polymer-based therapeutics have recently become essential drug delivery biomaterials for various bioactive compounds. Biodegradable and biocompatible polymer-based biomaterials fulfill the requirements of these therapeutics because they enable to obtain polymer biomaterials with optimized blood circulation, pharmacokinetics, biodegradability, and renal excretion. Herein, we describe an adaptable polymerization platform employed for the synthesis of long-circulating, stimulus-sensitive and biodegradable biomaterials, therapeutics, or theranostics. Four chain transfer agents (CTA) were designed and successfully synthesized for the reversible addition-fragmentation chain transfer polymerization, allowing the straightforward synthesis of hydrolytically biodegradable structures of block copolymers-based biomaterials. The controlled polymerization using the CTAs enables controlling the half-life of the hydrolytic degradation of polymer precursors in a wide range from 5 h to 21 days. Moreover, the antitumor drug pirarubicin (THP) was successfully conjugated to the polymer biomaterials via a pH-sensitive hydrazone bond for in vitro and in vivo experiments. Polymer conjugates demonstrated superior antitumor efficacy compared to basic linear polymer-based conjugates. Notably, the biodegradable systems, even though those with degradation in the order of hours were selected, increased the half-life of THP in the bloodstream almost two-fold. Indeed, the presented platform design enables the main chain-end specific attachment of targeting ligands or diagnostic molecules. The adaptable polymerization platform design allows tuning of the biodegradability rate, stimuli-sensitive drug bonding, and optimized pharmacokinetics to increase the therapy outcome and system targeting, thus allowing the preparation of targeted or theranostic polymer conjugates. Pracoviště Ústav makromolekulární chemie Kontakt Eva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358 Rok sběru 2024 Elektronická adresa https://www.sciencedirect.com/science/article/pii/S174270612300538X?via%3Dihub
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