Metastatic spread inhibition of cancer cells through stimuli-sensitive HPMA copolymer-bound actinonin nanomedicines

0559474 - ÚMCH 2023 RIV US eng J - Journal Article
Kousalová, Jana - Šírová, Milada - Kostka, Libor - Šubr, Vladimír - Kovářová, Jiřina - Běhalová, Kateřina - Studenovský, Martin - Kovář, Marek - Etrych, Tomáš
Metastatic spread inhibition of cancer cells through stimuli-sensitive HPMA copolymer-bound actinonin nanomedicines.
Nanomedicine: Nanotechnology, Biology and Medicine. Roč. 44, August (2022), č. článku 102578. ISSN 1549-9634. E-ISSN 1549-9642
R&D Projects: GA MŠMT(CZ) LTAUSA18083
Grant - others:AV ČR(CZ) JSPS-22-01
Program: Bilaterální spolupráce
Institutional support: RVO:61389013 ; RVO:61388971
Keywords : matrix metalloproteinases * metastases * actinonin
OECD category: Polymer science; Oncology (MBU-M)
Impact factor: 5.4, year: 2022
Method of publishing: Limited access
https://www.sciencedirect.com/science/article/pii/S1549963422000648?via%3Dihub

The unresolved task of modern medicine is to prevent metastatic spread during and after the treatment of primary tumors. Here, the design, controlled synthesis, in-depth physicochemical and biological characteristics of a novel panel of well-defined water-soluble copolymer conjugates bearing actinonin intended for advanced drug delivery and inhibition of metastatic spread are described. Three different synthetic approaches were employed to covalently attach actinonin to the N-(2-hydroxypropyl)methacrylamide copolymers to control the release of actinonin to its pharmacologically active form. Actinonin was attached to the polymers via hydroxamate group suppressing its activity during the delivery, with the activity restored after its release in the primary tumors or metastatic foci. Importantly, developed nanosystems with favorable drug release kinetics inhibited the metastatic spread of cancer cells from primary 4T1 tumors into the lungs as well as invasion of B16F10 melanoma cells from circulation into the lungs at the dosage without any sign of toxicity.
Permanent Link: https://hdl.handle.net/11104/0332758