title: 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.
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.
authors.affiliation: Department of Biotechnology, Ming Chuan University, Taoyuan, Taiwan, People's Republic of China.
authors.forename: Chung-Ming
authors.initials: CM
authors.lastname: Lin
authors.forename: Wei-Chien
authors.initials: WC
authors.lastname: Kao
authors.forename: Chun-An
authors.initials: CA
authors.lastname: Yeh
authors.forename: Hui-Jye
authors.initials: HJ
authors.lastname: Chen
authors.forename: Shinn-Zong
authors.initials: SZ
authors.lastname: Lin
authors.forename: Hsien-Hsu
authors.initials: HH
authors.lastname: Hsieh
authors.forename: Wei-Shen
authors.initials: WS
authors.lastname: Sun
authors.forename: Chih-Hsuan
authors.initials: CH
authors.lastname: Chang
authors.forename: Huey-Shan
authors.initials: HS
authors.lastname: Hung
mesh_terms: D001564:Benzo(a)pyrene / Q000633:toxicity; D001672:Biocompatible Materials; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems / Q000295:instrumentation*; D006046:Gold / Q000737:chemistry*; D006801:Humans; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid / Q000737:chemistry*; D051034:Inhibitor of Apoptosis Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000139:chemically induced / Q000188:drug therapy*; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000627:therapeutic use*; D017382:Reactive Oxygen Species
chemical_list: D001672:Biocompatible Materials; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D051034:Inhibitor of Apoptosis Proteins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D001564:Benzo(a)pyrene; D006046:Gold; D006820:Hyaluronic Acid