Qu Qiuyu, Ma Xing, Zhao Yanli
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, 637371 Singapore.
Nanoscale. 2015 Oct 28;7(40):16677-86. doi: 10.1039/c5nr05139h. Epub 2015 Sep 24.
A lot of investigations have been conducted using mesoporous silica nanoparticles (MSNPs) functionalized with different targeting ligands in order to deliver various hydrophobic and hydrophilic drugs to targeted cancer cells. However, the utilization of MSNPs to deliver drug molecules to targeted subcellular organelles has been rarely reported. In this work, we applied targeting ligand-conjugated MSNPs with an average diameter of 80 nm to deliver the anticancer drug doxorubicin (DOX) to mitochondria. Triphenoylphosphonium (TPP) was functionalized on MSNPs as a mitochondria targeting ligand. Mitochondria targeting efficiency was demonstrated in HeLa cells by a co-localization study of mitochondria and functionalized MSNPs as well as by fluorescence analysis in isolated mitochondria. In addition, enhanced cancer cell killing efficacy was achieved when using DOX-loaded and TPP-functionalized MSNPs for mitochondria-targeted delivery. Lowered adenosine triphosphate (ATP) production and decreased mitochondrial membrane potential were observed, demonstrating the mitochondria dysfunction caused by delivered DOX. The positive results indicate promising application potential of MSNPs in targeted subcellular drug delivery.
为了将各种疏水性和亲水性药物递送至靶向癌细胞，人们已经开展了大量使用不同靶向配体功能化的介孔二氧化硅纳米颗粒（MSNP）的研究。然而，利用MSNP将药物分子递送至靶向亚细胞器的报道却很少。在这项工作中，我们应用平均直径为80nm的靶向配体偶联的MSNP将抗癌药物阿霉素（DOX）递送至线粒体。三苯甲酰基鏻（TPP）作为线粒体靶向配体在MSNP上进行了功能化。通过线粒体与功能化MSNP的共定位研究以及分离线粒体中的荧光分析，在HeLa细胞中证明了线粒体靶向效率。此外，当使用负载DOX且TPP功能化的MSNP进行线粒体靶向递送时，实现了增强的癌细胞杀伤效果。观察到三磷酸腺苷（ATP）产生降低以及线粒体膜电位降低，证明了递送的DOX导致的线粒体功能障碍。这些阳性结果表明MSNP在靶向亚细胞药物递送中具有广阔的应用潜力。
