具有线粒体靶向功能的穿心莲内酯TPP-PEG-PE脂质体的制备及其作用于胃癌模型小鼠的机制研究

目的 制备穿心莲内酯(andrographolide,AP)(3-丙羧基)三苯基溴化膦[(3-carboxy propyl)triphenylphosph-onium bromide,TPP]-聚乙二醇(polyethylene glycol,PEG)-聚乙烯(polyethylene,PE)脂质体(AP@TPP-PE...

Preparation of andrographolide TPP-PEG-PE liposomes with mitochondrial targeting function and its mechanism in gastric cancer model mice

Objective To prepare andrographolide (AP) triphenyl phosphate (TPP)-polyethylene glycol (PEG)-polyethylene (PE) liposomes (AP@TPP-PEG-PE#Lips), and study its in vitro release, hemolysis, mitochondrial targeting, the mechanism of promoting gastric cancer cell apoptosis and acting on gastric cancer model mice. Methods The membrane hydration method was used to prepare AP@TPP-PEG-PE#Lips; The particle size, electric potential, micro-electron microscopic morphology, stability, hemolysis and in vitro release of the liposomes were detected; Flow cytometry was used to measure the uptake of gastric cancer cells to liposomes, and laser confocal microscopy to study its mitochondrial targeting; AP@TPP-PEG-PE#Lips in gastric cancer cells and effects of apoptosis and gastric cancer model mice were evaluated. Results The particle size of AP@TPP-PEG-PE#Lips is (23.8 ±1.7) nm, the Zeta potential is (30.2 ±1.1) mV, the distribution is relatively uniform, and the regular spherical structure; In vitro tests showed that AP@TPP-PEG- PE#Lips had low hemolysis rate, sustained release performance and good blood compatibility; Fluorescence test results showed that TPP-PEG-PE#Lips can promote the cellular uptake of drugs; AP@TPP-PEG-PE#Lips act on gastric cancer cells and gastric cancer model mice, the results showed that AP@TPP-PEG-PE#Lips can significantly reduce the mitochondrial membrane potential of gastric cancer cells, increase intracellular reactive oxygen species (ROS) content, and promote cysteine The release of Caspase-3 increased the pro-apoptotic protein B lymphocyte tumor-2 (Bcl-2) and decreased the expression of anti-apoptotic BCL2-Associated X (Bax) protein (P < 0.05). Conclusion AP@TPP-PEG-PE#Lips can effectively deliver the drug to the mitochondria and enhance the drug''s effect of promoting tumor cell apoptosis.