0618471 - MBÚ 2026 RIV NL eng J - Článek v odborném periodiku
Kaňa, Martin - Braunová, Alena - Starenko, Daniil - Frejková, Markéta - Bouček, Jan - Říhová, Blanka - Kovář, Marek - Etrych, Tomáš - Šírová, Milada
Overcoming P-glycoprotein-mediated multidrug resistance in cancer cells through micelle-forming PHPMA-b-PPO diblock copolymers for doxorubicin delivery.
Journal of Controlled Release. Roč. 381, May 10 (2025), č. článku 113645. ISSN 0168-3659. E-ISSN 1873-4995
Grant CEP: GA MZd(CZ) NU21-03-00273; GA MŠMT LX22NPO5102
Institucionální podpora: RVO:61388971 ; RVO:61389013
Klíčová slova: Multidrug resistance * P-glycoprotein inhibition * Sensitization to chemotherapy * Intracellular ATP depletion * HPMA copolymer * PPO * Diblock copolymers * Drug delivery system
Obor OECD: Immunology; Polymer science (UMCH-V)
Impakt faktor: 10.5, rok: 2023 ; AIS: 1.79, rok: 2023
Způsob publikování: Open access
Web výsledku:
https://www.sciencedirect.com/science/article/pii/S0168365925002652DOI: https://doi.org/10.1016/j.jconrel.2025.113645

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.
Trvalý link: https://hdl.handle.net/11104/0365334