Simultaneous delivery of doxorubicin and protease inhibitor derivative to solid tumors via star-shaped polymer nanomedicines overcomes P-gp- and STAT3-mediated chemoresistance

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F22%3A00558142" target="_blank" >RIV/61388971:_____/22:00558142 - isvavai.cz</a>
Alternative codes found
RIV/61389013:_____/22:00558142 RIV/68378050:_____/22:00558142
Result on the web
<a href="https://pubs.acs.org/doi/10.1021/acs.biomac.2c00256" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.biomac.2c00256</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.biomac.2c00256" target="_blank" >10.1021/acs.biomac.2c00256</a>

Result language
angličtina
Original language name
Simultaneous delivery of doxorubicin and protease inhibitor derivative to solid tumors via star-shaped polymer nanomedicines overcomes P-gp- and STAT3-mediated chemoresistance
Original language description
The derivative of protease inhibitor ritonavir (5-methyl-4-oxohexanoic acid ritonavir ester, RD) was recently recognized as a potent P-gp inhibitor and cancerostatic drug inhibiting the proteasome and STAT3 signaling. Therefore, we designed high-molecular-weight HPMA copolymer conjugates with a PAMAM dendrimer core bearing both doxorubicin (Dox) and RD (Star-RD + Dox) to increase the circulation half-life to maximize simultaneous delivery of Dox and RD into the tumor. Star-RD inhibited P-gp activity, potently sensitizing both low- and high-P-gp-expressing cancer cells to the cytostatic and proapoptotic activity of Dox in vitro. Star-RD + Dox possessed higher cytostatic and proapoptotic activities compared to Star-Dox and the equivalent mixture of Star-Dox and Star-RD in vitro. Star-RD + Dox efficiently inhibited STAT3 signaling and induced caspase-3 activation and DNA fragmentation in cancer cells in vivo. Importantly, Star-RD + Dox was found to have superior antitumor activity in terms of tumor growth inhibition and increased survival of mice bearing P-gp-expressing tumors.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10606 - Microbiology

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

Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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