期刊
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
卷 44, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.nano.2022.102578
关键词
Matrix metalloproteinases; Metastases; Actinonin; pH-sensitive release; Polymer conjugate
资金
- Czech Academy of Science [JSPS-22-01]
- Ministry of Education, Youth and Sports of the Czech Republic [LTAUSA18083]
- Institutional Research Concept [RVO 61388971]
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据