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

被引：41

作者：

Lin, Chung-Ming ^{[1
]}

Kao, Wei-Chien ^{[2
]}

Yeh, Chun-An ^{[2
]}

Chen, Hui-Jye ^{[2
]}

Lin, Shinn-Zong ^{[3
,4
,5
]}

Hsieh, Hsien-Hsu ^{[6
]}

Sun, Wei-Shen ^{[2
]}

Chang, Chih-Hsuan ^{[2
]}

Hung, Huey-Shan ^{[2
,3
]}

机构：

[1] Ming Chuan Univ, Dept Biotechnol, Taoyuan, Taiwan

[2] China Med Univ, Grad Inst Basic Med Sci, Taichung, Taiwan

[3] China Med Univ Hosp, Ctr Neuropsychiat, Taichung, Taiwan

[4] China Med Univ, Grad Inst Immunol, Taichung, Taiwan

[5] China Med Univ Beigang Hosp, Yunlin, Taiwan

[6] Taichung Vet Gen Hosp, Blood Bank, Taichung, Taiwan

来源：

NANOTECHNOLOGY | 2015年 / 26卷 / 10期

关键词：

hyaluronic acid-gold nanoparticle (AuNP-HA); inhibitor of apoptosis protein-2 (IAP-2) siRNA; benzo[a]pyrene (BaP); COOKING OIL FUMES; COATED GOLD NANOPARTICLES; SMALL INTERFERING RNA; ANTITUMOR-ACTIVITY; TUMOR-MODELS; THERAPY; SURFACE; NANOCARRIERS; DOXORUBICIN; CASPASES;

D O I：

10.1088/0957-4484/26/10/105101

中图分类号：

TB3 [工程材料学];

学科分类号：

0805 ; 080502 ;

摘要：

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.

引用

页数：20