DNA-Hybrid-Gated Photothermal Mesoporous Silica Nanoparticles for NIR-Responsive and Aptamer-Targeted Drug Delivery

详细信息    查看全文

• 作者：Yuanxin Zhang ; Zhiyao Hou ; Yakun Ge ; Kerong Deng ; Bei Liu ; Xuejiao Li ; Quanshun Li ; Ziyong Cheng ; Ping鈥檃n Ma ; Chunxia Li ; Jun Lin
• 刊名：ACS Applied Materials & Interfaces
• 出版年：2015
• 出版时间：September 23, 2015
• 年：2015
• 卷：7
• 期：37
• 页码：20696-20706
• 全文大小：707K
• ISSN：1944-8252

文摘

Near-infrared light is an attractive stimulus due to its noninvasive and deep tissue penetration. Particularly, NIR light is utilized for cancer thermotherapy and on-demand release of drugs by the disruption of the delivery carriers. Here we have prepared a novel NIR-responsive DNA-hybrid-gated nanocarrier based on mesoporous silica-coated Cu_1.8S nanoparticles. Cu_1.8S nanoparticles, possessing high photothermal conversion efficiency under a 980 nm laser, were chosen as photothermal agents. The mesoporous silica structure could be used for drug storage/delivery and modified with aptamer-modified GC-rich DNA-helix as gatekeepers, drug vectors, and targeting ligand. Simultaneously, the as-produced photothermal effect caused denaturation of DNA double strands, which triggered the drug release of the DNA-helix-loaded hydrophilic drug doxorubicin and mesopore-loaded hydrophobic drug curcumin, resulting in a synergistic therapeutic effect. The Cu_1.8S@mSiO₂ nanocomposites endocytosed by cancer cells through the aptamer-mediated mode are able to generate rational release of doxorubicin/curcumin under NIR irradiation, strongly enhancing the synergistic growth-inhibitory effect of curcumin against doxorubicin in MCF-7 cells, which is associated with a strong mitochondrial-mediated cell apoptosis progression. The underlying mechanism of apoptosis showed a strong synergistic inhibitory effect both on the expression of Bcl-2, Bcl-xL, Mcl-1, and upregulated caspase 3/9 activity and on the expression level of Bak and Bax. Therefore, Cu_1.8S@mSiO₂ with efficient synergistic therapeutic efficiency is a potential multifunctional cancer therapy nanoplatform.