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Membrane permeability and responsiveness drive performance: linking structural features with the antitumor effectiveness of doxorubicin-loaded stimuli-triggered polymersomes

  1. 1.
    0587483 - ÚMCH 2025 RIV US eng J - Článek v odborném periodiku
    Jäger, Eliezer - Černoch, Peter - Vragović, Martina - Calumby Albuquerque, Lindomar J. - Sincari, Vladimir - Heizer, T. - Jäger, Alessandro - Kučka, Jan - Šebestová Janoušková, Olga - Pavlova, Ewa - Šefc, L. - Giacomelli, F. C.
    Membrane permeability and responsiveness drive performance: linking structural features with the antitumor effectiveness of doxorubicin-loaded stimuli-triggered polymersomes.
    Biomacromolecules. Roč. 25, č. 7 (2024), s. 4192-4202. ISSN 1525-7797. E-ISSN 1526-4602
    Grant CEP: GA ČR(CZ) GC20-15479J; GA MŠMT(CZ) LM2023053; GA MŠMT(CZ) EH22_008/0004607; GA ČR(CZ) GJ20-15077Y
    Institucionální podpora: RVO:61389013
    Klíčová slova: polymersomes * permeability * responsiveness
    Obor OECD: Polymer science
    Impakt faktor: 5.5, rok: 2023 ; AIS: 1.018, rok: 2023
    Způsob publikování: Open access
    Web výsledku:
    https://pubs.acs.org/doi/10.1021/acs.biomac.4c00282DOI: https://doi.org/10.1021/acs.biomac.4c00282

    The permeability and responsiveness of polymer membranes are absolutely relevant in the design of polymersomes for cargo delivery. Accordingly, we herein correlate the structural features, permeability, and responsiveness of doxorubicin-loaded (DOX-loaded) nonresponsive and stimuli-responsive polymersomes with their in vitro and in vivo antitumor performance. Polymer vesicles were produced using amphiphilic block copolymers containing a hydrophilic poly[N-(2-hydroxypropyl)methacrylamide] (PHPMA) segment linked to poly[N-(4-isopropylphenylacetamide)ethyl methacrylate] (PPPhA, nonresponsive block), poly[4-(4,4,5,5-tetra-methyl-1,3,2-dioxaborolan-2-yl)benzyl methacrylate] [PbAPE, reactive oxygen species (ROS)-responsive block], or poly[2-(diisopropylamino)ethyl methacrylate] (PDPA, pH-responsive block). The PDPA-based polymersomes demonstrated outstanding biological performance with antitumor activity notably enhanced compared to their counterparts. We attribute this behavior to a fast-triggered DOX release in acidic tumor environments as induced by pH-responsive polymersome disassembly at pH < 6.8. Possibly, an insufficient ROS concentration in the selected tumor model attenuates the rate of ROS-responsive vesicle degradation, whereas the nonresponsive nature of the PPPhA block remarkably impacts the performance of such potential nanomedicines.
    Trvalý link: https://hdl.handle.net/11104/0355006
     
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