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

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10404 - Polymer science

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

Molecular Pharmaceutics

ISSN

1543-8384

e-ISSN

—

Svazek periodika

16

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

8

Strana od-do

3452-3459

Kód UT WoS článku

000480371700012

EID výsledku v databázi Scopus

2-s2.0-85070856390