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

Autor: Michal Pechar, Robert Pola, Martin Studenovský, Markéta Bláhová, Eliška Grosmanová, Aneta Dydowiczová, Marcela Filipová, Rayhanul Islam, Shanghui Gao, Jun Fang, Tomáš Etrych
Rok vydání: 2022
Předmět:
Zdroj: Nanomedicine: Nanotechnology, Biology and Medicine. 46:102597
ISSN: 1549-9634
DOI: 10.1016/j.nano.2022.102597
Popis: 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.
Databáze: OpenAIRE
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