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Overcoming multidrug resistance in Dox-resistant neuroblastoma cell lines via treatment with HPMA copolymer conjugates containing anthracyclines and P-gp inhibitors

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F16%3A00459478" target="_blank" >RIV/61389013:_____/16:00459478 - isvavai.cz</a>

  • Alternative codes found

    RIV/61388971:_____/16:00459478 RIV/00216208:11130/16:10324754 RIV/00064203:_____/16:10324754

  • Result on the web

    <a href="http://dx.doi.org/10.1016/j.jconrel.2016.05.036" target="_blank" >http://dx.doi.org/10.1016/j.jconrel.2016.05.036</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1016/j.jconrel.2016.05.036" target="_blank" >10.1016/j.jconrel.2016.05.036</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Overcoming multidrug resistance in Dox-resistant neuroblastoma cell lines via treatment with HPMA copolymer conjugates containing anthracyclines and P-gp inhibitors

  • Original language description

    Water-soluble N-(2-hydroxypropyl)methacrylamide copolymer conjugates bearing the anticancer drugs doxorubicin (Dox) or pirarubicin (THP), P-gp inhibitors derived from reversin 121 (REV) or ritonavir (RIT)), or both anticancer drug and P-gp inhibitor were designed and synthesized. All biologically active molecules were attached to the polymer carrier via pH-sensitive spacer enabling controlled release in mild acidic environment modeling endosomes and lysosomes of tumor cells. The cytotoxicity of the conjugates against three sensitive and Dox-resistant neuroblastoma (NB) cell lines, applied alone or in combination, was studied in vitro. All conjugates containing THP displayed higher cytotoxicity against all three Dox-resistant NB cell lines compared with the corresponding Dox-containing conjugates. Furthermore, the cytotoxicity of conjugates containing both drug and P-gp inhibitor was up to 10 times higher than that of the conjugate containing only drug. In general, the polymer-drug conjugates showed higher cytotoxicity when conjugates containing inhibitors were added 8 or 16 h prior to treatment compared with conjugates bearing both the inhibitor and the drug. The difference in cytotoxicity was more pronounced at the 16-h time point. Moreover, higher inhibitor:drug ratios resulted in higher cytotoxicity. The cytotoxicity of the polymer-drug used in combination with polymer P-gp inhibitor was up to 84 times higher than that of the polymer-drug alone.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

  • CEP classification

    CD - Macromolecular chemistry

  • OECD FORD branch

Result continuities

  • Project

    Result was created during the realization of more than one project. More information in the Projects tab.

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2016

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Journal of Controlled Release

  • ISSN

    0168-3659

  • e-ISSN

  • Volume of the periodical

    233

  • Issue of the periodical within the volume

    10 July

  • Country of publishing house

    NL - THE KINGDOM OF THE NETHERLANDS

  • Number of pages

    11

  • Pages from-to

    136-146

  • UT code for WoS article

    000378056400015

  • EID of the result in the Scopus database

    2-s2.0-84971232034