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Tumor stimulus-responsive biodegradable diblock copolymer conjugates as efficient anti-cancer nanomedicines
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SYSNO ASEP 0556939 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Tumor stimulus-responsive biodegradable diblock copolymer conjugates as efficient anti-cancer nanomedicines Author(s) Šubr, Vladimír (UMCH-V) RID, ORCID
Pola, Robert (UMCH-V) RID, ORCID
Gao, S. (JP)
Islam, R. (JP)
Hirata, T. (JP)
Miyake, D. (JP)
Koshino, K. (JP)
Zhou, J.-R. (JP)
Yokomizo, K. (JP)
Fang, J. (JP)
Etrych, Tomáš (UMCH-V) RID, ORCIDArticle number 698 Source Title Journal of Personalized Medicine. - : MDPI
Roč. 12, č. 5 (2022)Number of pages 18 s. Language eng - English Country CH - Switzerland Keywords pirarubicin ; drug delivery ; HPMA conjugate Subject RIV CD - Macromolecular Chemistry OECD category Polymer science R&D Projects LTAUSA18083 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support UMCH-V - RVO:61389013 UT WOS 000801380300001 EID SCOPUS 85129837930 DOI 10.3390/jpm12050698 Annotation Biodegradable nanomedicines are widely studied as candidates for the effective treatment of various cancerous diseases. Here, we present the design, synthesis and evaluation of biodegradable polymer-based nanomedicines tailored for tumor-associated stimuli-sensitive drug release and polymer system degradation. Diblock polymer systems were developed, which enabled the release of the carrier drug, pirarubicin, via a pH-sensitive spacer allowing for the restoration of the drug cytotoxicity solely in the tumor tissue. Moreover, the tailored design enables the matrix-metalloproteinases- or reduction-driven degradation of the polymer system into the polymer chains excretable from the body by glomerular filtration. Diblock nanomedicines take advantage of an enhanced EPR effect during the initial phase of nanomedicine pharmacokinetics and should be easily removed from the body after tumor microenvironment-associated biodegradation after fulfilling their role as a drug carrier. In parallel with the similar release profiles of diblock nanomedicine to linear polymer conjugates, these diblock polymer conjugates showed a comparable in vitro cytotoxicity, intracellular uptake, and intratumor penetration properties. More importantly, the diblock nanomedicines showed a remarkable in vivo anti-tumor efficacy, which was far more superior than conventional linear polymer conjugates. These findings suggested the advanced potential of diblock polymer conjugates for anticancer polymer therapeutics. Workplace Institute of Macromolecular Chemistry Contact Eva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358 Year of Publishing 2023 Electronic address https://www.mdpi.com/2075-4426/12/5/698
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