1. Hyaluronic acid-fabricated nanogold delivery of the inhibitor of apoptosis protein-2 siRNAs inhibits benzo[a]pyrene-induced oncogenic properties of lung cancer A549 cells
- Author
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Shinn Zong Lin, Chung Ming Lin, Chih Hsuan Chang, Huey Shan Hung, Hui Jye Chen, Hsien Hsu Hsieh, Chun An Yeh, Wei Chien Kao, and Wei Shen Sun
- Subjects
Small interfering RNA ,Lung Neoplasms ,Materials science ,Cell Survival ,Biocompatible Materials ,Bioengineering ,Inhibitor of apoptosis ,Inhibitor of Apoptosis Proteins ,chemistry.chemical_compound ,Drug Delivery Systems ,Cell Line, Tumor ,Benzo(a)pyrene ,Humans ,General Materials Science ,Hyaluronic Acid ,RNA, Small Interfering ,Electrical and Electronic Engineering ,Fluorescein isothiocyanate ,A549 cell ,Cell growth ,Mechanical Engineering ,General Chemistry ,Molecular biology ,Hyaluronan Receptors ,chemistry ,Mechanics of Materials ,Cell culture ,Apoptosis ,Cancer cell ,Nanoparticles ,Gold ,Reactive Oxygen Species - Abstract
Benzo[a]pyrene (BaP), a component of cooking oil fumes (COF), promotes lung cancer cell proliferation and survival via the induction of inhibitor of apoptosis protein-2 (IAP-2) proteins. Thus knockdown of IAP-2 would be a promising way to battle against lung cancer caused by COF. Functionalized gold nanoparticle (AuNP) is an effective delivery system for bio-active materials. Here, biocompatible hyaluronic acid (HA) was fabricated into nanoparticles to increase the target specificity by binding to CD44-over-expressed cancer cells. IAP-2-specific small-interfering RNA (siRNAs) or fluorescein isothiocyanate (FITC) were then incorporated into AuNP-HA. Conjugation of IAP-2 siRNA into AuNPs-HA was verified by the UV-vis spectrometer and Fourier transform infrared spectrometer. Further studies showed that AuNP-HA/FITC were effectively taken up by A549 cells through CD44-mediated endocytosis. Incubation of BaP-challenged cells with AuNP-HA-IAP-2 siRNAs silenced the expression of IAP-2, decreased cell proliferation and triggered pronounced cell apoptosis by the decrease in Bcl-2 protein and the increase in Bax protein as well as the active form of caspases-3. The BaP-elicited cell migration and enzymatic activity of the secreted matrix metalloproteinase-2 were also substantially suppressed by treatment with AuNP-HA-IAP-2 siRNAs. These results indicated that IAP-2 siRNAs can be efficiently delivered into A549 cells by functionalized AuNP-HA to repress the IAP-2 expression and BaP-induced oncogenic events, suggesting the potential therapeutic application of IAP-2 siRNA or other siRNA-conjugated AuNP-HA composites to COF-induced lung cancer and other gene-caused diseases in the future.
- Published
- 2015