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Overcoming P-glycoprotein-mediated multidrug resistance in cancer cells through micelle-forming PHPMA-b-PPO diblock copolymers for doxorubicin delivery
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SYSNO ASEP 0618471 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Overcoming P-glycoprotein-mediated multidrug resistance in cancer cells through micelle-forming PHPMA-b-PPO diblock copolymers for doxorubicin delivery Author(s) Kaňa, Martin (MBU-M) ORCID
Braunová, Alena (UMCH-V) RID
Starenko, Daniil (MBU-M)
Frejková, Markéta (UMCH-V) RID, ORCID
Bouček, Jan (MBU-M)
Říhová, Blanka (MBU-M) RID
Kovář, Marek (MBU-M) RID, ORCID
Etrych, Tomáš (UMCH-V) RID, ORCID
Šírová, Milada (MBU-M) RID, ORCIDArticle number 113645 Source Title Journal of Controlled Release. - : Elsevier - ISSN 0168-3659
Roč. 381, May 10 (2025)Number of pages 17 s. Language eng - English Country NL - Netherlands Keywords Multidrug resistance ; P-glycoprotein inhibition ; Sensitization to chemotherapy ; Intracellular ATP depletion ; HPMA copolymer ; PPO ; Diblock copolymers ; Drug delivery system OECD category Immunology R&D Projects NU21-03-00273 GA MZd - Ministry of Health (MZ) LX22NPO5102 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support MBU-M - RVO:61388971 ; UMCH-V - RVO:61389013 UT WOS 001457041100001 EID SCOPUS 105000612958 DOI https://doi.org/10.1016/j.jconrel.2025.113645 Annotation Multidrug resistance (MDR) represents one of the major concerns in cancer therapy as it may cause reduced efficacy of chemotherapeutic drugs. The study explores the potential of novel amphiphilic diblock (DB) micelle forming copolymers composed of poly[N-(2-hydroxypropyl)methacrylamide]-based copolymers and poly(propylene oxide) to overcome MDR mechanisms. The DB copolymers and their doxorubicin (Dox) conjugates significantly inhibited drug efflux in chemoresistant cancer cells by depletion of intracellular ATP, resulting in increased Dox accumulation. Mechanisms involved in MDR inhibition are shown. Copolymers with additionally loaded PPO in the micelle core demonstrated superior efficacy in vitro and in vivo in treatment of experimental murine tumor CT26. The ATP depletion capacity was also demonstrátor in patient-derived xenograft (PDX) model. Workplace Institute of Microbiology Contact Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Year of Publishing 2026 Electronic address https://www.sciencedirect.com/science/article/pii/S0168365925002652
Number of the records: 1