Polymer nanomedicines with enzymatically triggered activation: a comparative study of in vitro and in vivo anti-cancer efficacy related to the spacer structure

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F22%3A00561407" target="_blank" >RIV/61389013:_____/22:00561407 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S1549963422000831" target="_blank" >https://www.sciencedirect.com/science/article/pii/S1549963422000831</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.nano.2022.102597" target="_blank" >10.1016/j.nano.2022.102597</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Polymer nanomedicines with enzymatically triggered activation: a comparative study of in vitro and in vivo anti-cancer efficacy related to the spacer structure

Popis výsledku v původním jazyce

Polymer nanomedicines with anti-tumor activity should exhibit sufficient stability during systemic circulation to the target tissue. However, they should release the active drug selectively in the tumor. Thus, choice of a tumor-specific stimuli-sensitive spacer between the drug and the carrier is critical. Here, a series of polymer conjugates of anti-cancer drugs doxorubicin and pirarubicin covalently bound to copolymers based on N-(2-hydroxypropyl)methacrylamide via various enzymatically cleavable oligopeptide spacers were prepared and characterized. The highest rate of the drug release from the polymer carriers in presence of the lysosomal protease cathepsin B was determined for the copolymers with Val-Cit-Aba spacer. Copolymers containing pirarubicin were more cytotoxic and showed higher internalization rate than the corresponding doxorubicin counterparts. The conjugates containing GFLG and Val-Cit-Aba spacers exhibited the highest anti-tumor efficacy in vivo against murine sarcoma S-180, the highest rate of the enzymatically catalyzed drug release, and the highest cytotoxicity in vitro.

Název v anglickém jazyce

Polymer nanomedicines with enzymatically triggered activation: a comparative study of in vitro and in vivo anti-cancer efficacy related to the spacer structure

Popis výsledku anglicky

Polymer nanomedicines with anti-tumor activity should exhibit sufficient stability during systemic circulation to the target tissue. However, they should release the active drug selectively in the tumor. Thus, choice of a tumor-specific stimuli-sensitive spacer between the drug and the carrier is critical. Here, a series of polymer conjugates of anti-cancer drugs doxorubicin and pirarubicin covalently bound to copolymers based on N-(2-hydroxypropyl)methacrylamide via various enzymatically cleavable oligopeptide spacers were prepared and characterized. The highest rate of the drug release from the polymer carriers in presence of the lysosomal protease cathepsin B was determined for the copolymers with Val-Cit-Aba spacer. Copolymers containing pirarubicin were more cytotoxic and showed higher internalization rate than the corresponding doxorubicin counterparts. The conjugates containing GFLG and Val-Cit-Aba spacers exhibited the highest anti-tumor efficacy in vivo against murine sarcoma S-180, the highest rate of the enzymatically catalyzed drug release, and the highest cytotoxicity in vitro.

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

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

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

Název periodika

Nanomedicine: Nanotechnology, Biology and Medicine

ISSN

1549-9634

e-ISSN

1549-9642

Svazek periodika

46

Číslo periodika v rámci svazku

November

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

8

Strana od-do

102597

Kód UT WoS článku

000857250800002

EID výsledku v databázi Scopus

2-s2.0-85137272421