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

0561407 - ÚMCH 2023 RIV US eng J - Článek v odborném periodiku
Pechar, Michal - Pola, Robert - Studenovský, Martin - Bláhová, Markéta - Grosmanová, Eliška - Dydowiczová, Aneta - Filipová, Marcela - Islam, R. - Gao, S. - Fang, J. - Etrych, Tomáš
Polymer nanomedicines with enzymatically triggered activation: a comparative study of in vitro and in vivo anti-cancer efficacy related to the spacer structure.
Nanomedicine: Nanotechnology, Biology and Medicine. Roč. 46, November (2022), č. článku 102597. ISSN 1549-9634. E-ISSN 1549-9642
Grant CEP: GA ČR(CZ) GA22-12483S; GA MŠMT(CZ) LTAUSA18083
Grant ostatní: AV ČR(CZ) JSPS-22-01
Program: Bilaterální spolupráce
Institucionální podpora: RVO:61389013
Klíčová slova: drug delivery * polymer cancerostatics * enzymatic release
Obor OECD: Polymer science
Impakt faktor: 5.4, rok: 2022
Způsob publikování: Omezený přístup
https://www.sciencedirect.com/science/article/pii/S1549963422000831

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.
Trvalý link: https://hdl.handle.net/11104/0334099