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pH-responsive polymersome-mediated delivery of doxorubicin into tumor sites enhances the therapeutic efficacy and reduces cardiotoxic effects
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SYSNO ASEP 0541439 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title pH-responsive polymersome-mediated delivery of doxorubicin into tumor sites enhances the therapeutic efficacy and reduces cardiotoxic effects Author(s) Calumby Albuquerque, Lindomar J. (UMCH-V)
Sincari, Vladimir (UMCH-V) ORCID, RID
Jäger, Alessandro (UMCH-V) RID, ORCID
Kučka, Jan (UMCH-V) RID, ORCID
Humajová, J. (CZ)
Pankrác, J. (CZ)
Páral, P. (CZ)
Heizer, T. (CZ)
Janoušková, Olga (UMCH-V) RID, SAI, ORCID
Davidovich, I. (IL)
Talmon, Y. (IL)
Pouckova, P. (CZ)
Štěpánek, Petr (UMCH-V) RID, ORCID
Šefc, L. (CZ)
Hrubý, Martin (UMCH-V) RID, ORCID
Giacomelli, F. C. (BR)
Jäger, Eliezer (UMCH-V) ORCID, RIDSource Title Journal of Controlled Release. - : Elsevier - ISSN 0168-3659
Roč. 332, 10 April (2021), s. 529-538Number of pages 10 s. Language eng - English Country NL - Netherlands Keywords nanomedicine ; pH-responsive polymersomes ; doxorubicin Subject RIV CD - Macromolecular Chemistry OECD category Polymer science R&D Projects GJ20-15077Y GA ČR - Czech Science Foundation (CSF) GJ20-13946Y GA ČR - Czech Science Foundation (CSF) LM2018133 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LO1507 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LTC19032 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Research Infrastructure Czech-BioImaging II - 90129 - Ústav molekulární genetiky AV ČR, v. v. i. Method of publishing Limited access Institutional support UMCH-V - RVO:61389013 UT WOS 000646579700007 EID SCOPUS 85102645269 DOI 10.1016/j.jconrel.2021.03.013 Annotation The delivery of therapeutics into sites of action by using cargo-delivery platforms potentially minimizes their premature degradation and fast clearance from the bloodstream. Additionally, drug-loaded stimuli-responsive supramolecular assemblies can be produced to respond to the inherent features of tumor microenvironments, such as extracellular acidosis. We report in this framework the use of pH-responsive polymersomes (PSs) manufactured using poly([N-(2-hydroxypropyl)] methacrylamide)35-b-poly[2-(diisopropylamino)ethyl methacrylate]75 as the building unit (PHPMA35-b-PDPA75). The self-assemblies were produced with desired size towards long circulation time and tumor accumulation (hydrodynamic diameter - DH approximately 100 nm), and they could be successfully loaded with 10% w/w DOX (doxorubicin), while maintaining colloidal stability. The DOX loaded amount is presumably mainly burst-released at the acidic microenvironment of tumors thanks to the pH-switchable property of PDPA (pKa approximately 6.8), while reduced drug leakage has been monitored in pH 7.4. Compared to the administration of free DOX, the drug-loaded supramolecular structures greatly enhanced the therapeutic efficacy with effective growth inhibition of EL4 lymphoma tumor model and 100% survival rate in female C57BL/6 black mice over 40 days. The approach also led to reduced cardiotoxic effect. These features highlight the potential application of such nanotechnology-based treatment in a variety of cancer therapies where low local pH is commonly found, and emphasize PHPMA-based nanomedicines as an alternative to PEGylated formulations. Workplace Institute of Macromolecular Chemistry Contact Eva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358 Year of Publishing 2022 Electronic address https://www.sciencedirect.com/science/article/pii/S0168365921001243?via%3Dihub
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