Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 44, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.nano.2022.102578
Keywords
Matrix metalloproteinases; Metastases; Actinonin; pH-sensitive release; Polymer conjugate
Funding
- Czech Academy of Science [JSPS-22-01]
- Ministry of Education, Youth and Sports of the Czech Republic [LTAUSA18083]
- Institutional Research Concept [RVO 61388971]
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This study describes the design, synthesis, physicochemical and biological characteristics of water-soluble copolymer conjugates bearing actinonin for advanced drug delivery and inhibition of metastatic spread. The developed nanosystems showed favorable drug release kinetics and effectively inhibited the metastatic spread of cancer cells, highlighting their potential clinical application.
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.(c) 2022 Elsevier Inc. All rights reserved.
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