Studies on PEGylated Gold Nanoparticles Loaded with 5-Hydroxydecanoate for Chemo-Photothermal Therapy of Human Lung Adenocarcinomas In Vitro

Abstract

Gold nanoparticles ( Au NPs) have promising applications in the fields of drug delivery and photothermal therapy. 5-hydroxydecanoate (5-HD) is a kind of highly selective mitochondrial ATP sensitive potassium (mitoKATP) channel blocker. In this research, firstly, 5-HD was studied whether it could induce human lung adenocarcinomas (A549) cells apoptosis; secondly, PEGylated gold nanoparticles loaded with 5-HD ( Au NPs-PEG-5-HD) were prepared to develop a new chemotherapy and photothermal therapy in one system under the irradiation of green light-emitting diode (LED). Subsequently, in vitro cytotoxicity test was analyzed by cell counting kit-8 (CCK-8), the change of mitochondrial membrane potential (Δψm) was determined by immunofluorescence microscopy with R-123 fluorescence, and cell apoptosis and necrosis rate were detected by flow cytometry. The results of CCK8 revealed that the inhibition rates of A549 cells were all greatly increased when cells were treated with free 5-HD, free 5-HD +LED irradiation, Au NPs-PEG-5-HD and Au NPs-PEG-5-HD+LED irradiation, and Au NPs-PEG-5-HD had enhanced cell-killing effect compared with 5-HD, furthermore, the Au NPs-PEG-5-HD and LED irradiation played a very great synergy effect. The immunofluorescence microscopy data also exhibited a reduction of Δψm correspondingly. Flow cytometric analysis showed that the apoptosis rate of cells that were incubated with free 5-HD, 5-HD+LED irradiation, Au NPs-PEG-5-HD or Au NPs–PEG–5-HD+LED irradiation significantly increased to about 9.2%, 10.7%, 18.3% or 12.4% and the percentage of necrosis cells increased to around 8.8%, 9.7%, 48.0% or 69.8%, respectively. In a word, all the results indicated that the 5-HD had shown the ability to induce A549 cells apoptosis as a chemotherapy agent, and its ability would be improved when 5-HD is loaded on PEGylated Au NPs, as well as Au NPs-PEG-5-HD exhibited significantly enhanced photothermal effects for treatment of lung adenocarcinomas.