Liposome As Drug Delivery System Enhance Anticancer Activity Of Iridium (Iii) Complex

Herein an Ir(III) complex [Ir(Hppy)(2)(HMNPIP)](PF6) (Ir1, Hppy = 2-phenylpyridine, HMNPIP = 2-(1H-imidazo[4,5-f][1, 10]phenanthroline-3-yl)-6-methoxy-4-nitrophenol) was prepared and characterized. Due to the low anticancer activity ofIr1when administered free drug, we prepared a liposomeIr1Lipoencapsulated form ofIr1to improve the antitumor effect, furthermore, we explored the antitumor mechanism of both formsin vitroexperiments on HepG2 cells. We investigated the inhibitory efficiency ofIr1andIr1Lipoon 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. Anin vivostudy 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 liposomesIr1Lipodisplayed high potency against a variety of tumour cellsin vitro, especially against HepG2 (IC50= 4.6 +/- 0.5 mu M). Mechanism studies indicated thatIr1Lipoinitiated 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,Ir1Liposignificantly 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 ofIr1by a factor of relatively minor side effects.