Superior penetration and cytotoxicity of HPMA copolymer conjugates of pirarubicin in tumor cell spheroid

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F19%3A00507279" target="_blank" >RIV/61389013:_____/19:00507279 - isvavai.cz</a>
Result on the web
<a href="https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.9b00248" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.9b00248</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.molpharmaceut.9b00248" target="_blank" >10.1021/acs.molpharmaceut.9b00248</a>

Result language
angličtina
Original language name
Superior penetration and cytotoxicity of HPMA copolymer conjugates of pirarubicin in tumor cell spheroid
Original language description
N-(2-Hydroxypropyl)methacrylamide copolymer conjugates of pirarubicin (THP), P-THP, accumulates selectively in solid tumor tissue by the enhanced permeability and retention (EPR) effect. Despite of high accumulation in solid tumors, some macromolecular antitumor agents show poor therapeutic outcome because of poor tissue diffusion into the tumor as well as obstructed tumor blood flow. Here, we confirmed that cellular uptake of P-THP was 25 times less than that of free THP at 1–4 h incubation time in vitro. The passage of P-THP through the confluent tight-monolayer cells junction was 12 times higher than free THP, and P-THP penetrated deeper into the tumor cell spheroid (1.3–1.7-fold) than free THP in 4 h. In addition, P-THP showed cytotoxicity comparable to that of free THP to tumor-cells in spheroid form, despite of 7 times lower cytotoxicity of P-THP to the monolayer cells to that of free THP in vitro. These results indicate that P-THP administration can exhibit deeper diffusion into the tumor cell spheroid than free THP. As a consequence, P-THP exhibits more efficient antitumor activity than free THP in vivo, which is also supported by better pharmacokinetics and tumor accumulation of P-THP than free THP.
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
10404 - Polymer science

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)

Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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