Anticancer and Chemosensitizing Effects of Menadione-Containing Peptide-Targeted Solid Lipid Nanoparticles.

Autor:	Zoughaib M; Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlyovskaya St., 420008 Kazan, Russia; Scientific and Educational Center of Pharmaceutics, Kazan Federal University, 18 Kremlyovskaya St., 420008 Kazan, Russia. Electronic address: mohamadzougheib@gmail.com., Pashirova TN; Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, 8 Arbuzov St., 420088 Kazan, Russia., Nikolaeva V; Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlyovskaya St., 420008 Kazan, Russia; Scientific and Educational Center of Pharmaceutics, Kazan Federal University, 18 Kremlyovskaya St., 420008 Kazan, Russia., Kamalov M; Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlyovskaya St., 420008 Kazan, Russia; Scientific and Educational Center of Pharmaceutics, Kazan Federal University, 18 Kremlyovskaya St., 420008 Kazan, Russia., Nakhmetova F; Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlyovskaya St., 420008 Kazan, Russia; Scientific and Educational Center of Pharmaceutics, Kazan Federal University, 18 Kremlyovskaya St., 420008 Kazan, Russia., Salakhieva DV; Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlyovskaya St., 420008 Kazan, Russia; Scientific and Educational Center of Pharmaceutics, Kazan Federal University, 18 Kremlyovskaya St., 420008 Kazan, Russia., Abdullin TI; Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlyovskaya St., 420008 Kazan, Russia; Scientific and Educational Center of Pharmaceutics, Kazan Federal University, 18 Kremlyovskaya St., 420008 Kazan, Russia. Electronic address: tabdulli@gmail.com.
Jazyk:	angličtina
Zdroj:	Journal of pharmaceutical sciences [J Pharm Sci] 2024 Aug; Vol. 113 (8), pp. 2258-2267. Date of Electronic Publication: 2024 Mar 18.
DOI:	10.1016/j.xphs.2024.03.009
Abstrakt:	Vitamin K derivatives such as menadione (MD) have been recognized as promising redox-modulating and chemosensitizing agents for anticancer therapy, however, their cellular activities in peptide-targeted nanocarriers have not been elucidated to date. This study provides the guidelines for developing MD-loaded solid lipid nanoparticles (SLN) modified with extracellular matrix (ECM)-derived peptides. Relationships between RGD peptide concentration and changes in DLS characteristics as well as accumulation of SLN in cancer cells were revealed to adjust the peptide-lipid ratio. SLN system maintained adequate nanoparticle concentration and low dispersity after introduction of MD and MD/RGD, whereas formulated MD was protected from immediate conjugation with reduced glutathione (GSH). RGD-modified MD-containing SLN showed enhanced prooxidant, GSH-depleting and cytotoxic activities toward PC-3 prostate cancer cells attributed to improved cellular pharmacokinetics of the targeted formulation. Furthermore, this formulation effectively sensitized PC-3 cells and OVCAR-4 ovarian cancer cells to free doxorubicin and cisplatin so that cell growth was inhibited by MD-drug composition at nontoxic concentrations of the ingredients. These results provide an important background for further improving chemotherapeutic methods based on combination of conventional cytostatics with peptide-targeted SLN formulations of MD. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu