Liposome as drug delivery system enhance anticancer activity of iridium (III) complex. (2nd October 2021)

• Record Type: Journal Article
• Authors: Gu, Yiying; Bai, Lan; Zhang, Yuanyuan; Zhang, Huiwen; Xing, Degang; Tian, Li; Zhou, Yi; Hao, Jing; Liu, Yunjun
• Is Part Of: Journal of liposome research. Volume 31:Number 4(2021)
• Page Start: 342
• Page End: 355
• Publication Date: 2021-10-02
• Subjects: Iridium (III) complex -- liposome -- ROS -- mitochondria dysfunction -- apoptosis; Liposomes -- Periodicals; Liposomes -- Periodicals; 575.57
• DOI: 10.1080/08982104.2020.1818779
• Languages: English
• ISSNs: 0898-2104

Abstract

Abstract: Herein an Ir(III) complex [Ir(Hppy)2 (HMNPIP)](PF6 ) (Ir1, Hppy = 2-phenylpyridine, HMNPIP = 2-(1 H -imidazo[4, 5-f][1, 10]phenanthroline-3-yl)-6-methoxy-4-nitrophenol) was prepared and characterized. Due to the low anticancer activity of Ir1 when administered free drug, we prepared a liposome Ir1Lipo encapsulated form of Ir1 to improve the antitumor effect, furthermore, we explored the antitumor mechanism of both forms in vitro experiments on HepG2 cells. We investigated the inhibitory efficiency of Ir1 and Ir1Lipo on cell viability and proliferation using MTT (MTT = 3-(4, 5-dimethylthiazole)-2, 5-diphenltetraazolium bromide) and colony-forming assay. Intracellular accumulation of reactive oxygen species (ROS) was examined using a fluorescence microscope (High Content Screening System, ImageXpress Micro XLS System, Molecular Devices LLC, Sunnyvale, CA), programmed cell death cells stained with acridine orange/ethidium bromide (AO/EB) using flow cytometry detection and western blot have been performed. An in vivo study where HepG2 cells were transplanted into nude nice as xenografts. Tumour volume and body weight were monitored during the 10 days of administration. After encapsulation in liposomes Ir1Lipo displayed high potency against a variety of tumour cells in vitro, especially against HepG2 (IC50 = 4.6 ± 0.5 μM). Mechanism studies indicated that Ir1Lipo initiated apoptosis by generating intracellular ROS that regulate lysosomal-mitochondrial dysfunction, followed by microtubule disruption that subsequently leads to a G0/G1 phase of cell cycle arrest. Additionally, Ir1Lipo significantly curbed tumour growth in nude mice. The tumour inhibitory rate was 51.2% (5.6 mg/kg). Therefore, liposome as a drug delivery system greatly enhances anticancer activity of Ir1 by a factor of relatively minor side effects.