Nanotherapeutics with suitable properties for advanced anticancer therapy based on HPMA copolymer-bound ritonavir via pH-sensitive spacers
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F18%3A00492736" target="_blank" >RIV/61389013:_____/18:00492736 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1016/j.ejpb.2018.07.023" target="_blank" >http://dx.doi.org/10.1016/j.ejpb.2018.07.023</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.ejpb.2018.07.023" target="_blank" >10.1016/j.ejpb.2018.07.023</a>
Alternative languages
Result language
angličtina
Original language name
Nanotherapeutics with suitable properties for advanced anticancer therapy based on HPMA copolymer-bound ritonavir via pH-sensitive spacers
Original language description
Ritonavir (RIT) is a widely used antiviral drug that acts as an HIV protease inhibitor with emerging potential in anticancer therapies. RIT causes inhibition of P-glycoprotein, which plays an important role in multidrug resistance (MDR) in cancer cells when overexpressed. Moreover, RIT causes mitochondrial dysfunction, leading to decreased ATP production and reduction of caveolin I expression, which can affect cell migration and tumor progression. To increase its direct antitumor activity, decrease severe side effects induced by the use of free RIT and improve its pharmacokinetics, ritonavir 5-methyl-4-oxohexanoate (RTV) was synthesized and conjugated to a tumor-targeted polymer carrier based on a N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer. Here we demonstrated that polymer-bound RTV enhanced the internalization of polymer-RTV conjugates, differing in RTV content from 4 to 15 wt%, in HeLa cancer cells compared with polymer without RTV. The most efficient influx and internalization properties were determined for the polymer conjugate bearing 11 wt% of RTV. This conjugate was internalized by cells using both caveolin- and clathrin-dependent endocytic pathways in contrast to the RTV-free polymer, which was preferentially internalized only by clathrin-mediated endocytosis. Moreover, we found the co-localization of the RTV-conjugate with mitochondria and a significant decrease of ATP production in treated cells. Thus, the impact on mitochondrial mechanism can influence the function of ATP-dependent P-glycoprotein and also the cell viability of MDR cancer cells. Overall, this study demonstrated that the polymer-RTV conjugate is a promising polymer-based nanotherapeutic, suitable for antitumor combination therapy with other anticancer drugs and a potential mitochondrial drug delivery system.
Czech name
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Czech description
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Classification
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
10404 - Polymer science
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
European Journal of Pharmaceutics and Biopharmaceutics
ISSN
0939-6411
e-ISSN
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Volume of the periodical
131
Issue of the periodical within the volume
October
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
10
Pages from-to
141-150
UT code for WoS article
000446284400014
EID of the result in the Scopus database
2-s2.0-85051662941