Influence of Redox-Active Chitosan-Polyaminoxyl Micelles Loaded with Daunorubicin on Activity of Nrf2 Transcription Factor.

Autor: Balakina AA; Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Science, Chernogolovka, Moscow Region, Russia. balakina@icp.ac.ru.; P. G. Demidov Yaroslavl State University, Yaroslavl, Russia. balakina@icp.ac.ru., Amozova VI; Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Science, Chernogolovka, Moscow Region, Russia., Sen' VD; Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Science, Chernogolovka, Moscow Region, Russia.; P. G. Demidov Yaroslavl State University, Yaroslavl, Russia.
Jazyk: angličtina
Zdroj: Bulletin of experimental biology and medicine [Bull Exp Biol Med] 2024 Aug; Vol. 177 (4), pp. 569-577. Date of Electronic Publication: 2024 Sep 17.
DOI: 10.1007/s10517-024-06224-7
Abstrakt: A new system for delivery of anthracycline antibiotics based on chitosan-polyaminoxyls (CPA) was studied in a model of non-tumor (human embryonic mesenchymal stem cells) and tumor cells (human hepatocellular carcinoma) in vitro. The presence of CPA micelles considerably suppresses daunorubicin-induced ROS generation in normal cells without affecting this process in tumor cells. CPA micelles do not reduce the cytotoxic effect of daunorubicin and do not prevent its accumulation in cells. The use of CPA significantly increases accumulation of Nrf2 transcription factor in the nuclei of both normal and tumor cells in comparison with free daunorubicin. Increased nuclear translocation of Nrf2 leads to a significant increase in the expression of its target gene TXN1, but not the NQO1, GPX1, and HMOX1 genes, the increased expression of which can lead to the development of resistance to anthracycline antibiotics. Redox-active CPA micelles have great potential for the development of nanoparticles for the transport of anthracycline antibiotics in experimental tumor chemotherapy, and also as promising activators of Nrf2 transcription factor.
(© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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