Department of Chemistry, Shands Cancer Center, Center for Research at Bio/Nano Interface, University of Florida Genetics Institute, and McKnight Brain Institute, University of Florida, Gainesville, FL 32611-7200, USA.
Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):5-10. doi: 10.1073/pnas.0909611107. Epub 2009 Dec 22.
We report the design of a self-assembled aptamer-micelle nanostructure that achieves selective and strong binding of otherwise low-affinity aptamers at physiological conditions. Specific recognition ability is directly built into the nanostructures. The attachment of a lipid tail onto the end of nucleic acid aptamers provides these unique nanostructures with an internalization pathway. Other merits include: extremely low off rate once bound with target cells, rapid recognition ability with enhanced sensitivity, low critical micelle concentration values, and dual-drug delivery pathways. To prove the potential detection/delivery application of this aptamer-micelle in biological living systems, we mimicked a tumor site in the blood stream by immobilizing tumor cells onto the surface of a flow channel device. Flushing the aptamer-micelles through the channel demonstrated their selective recognition ability under flow circulation in human whole-blood sample. The aptamer-micelles show great dynamic specificity in flow channel systems that mimic drug delivery in the blood system. Therefore, our DNA aptamer-micelle assembly has shown high potential for cancer cell recognition and for in vivo drug delivery applications.
我们报告了一种自组装适体-胶束纳米结构的设计,该结构在生理条件下实现了低亲和力适体的选择性和强结合。特异性识别能力直接构建在纳米结构中。在核酸适体的末端连接脂质尾巴为这些独特的纳米结构提供了内化途径。其他优点包括:与靶细胞结合后极低的脱落率、具有增强敏感性的快速识别能力、低临界胶束浓度值和双重药物输送途径。为了证明这种适体-胶束在生物活体系统中的潜在检测/输送应用,我们通过将肿瘤细胞固定在流道装置的表面来模拟血液中的肿瘤部位。通过通道冲洗适体-胶束,在人全血样本的流动循环下证明了它们的选择性识别能力。适体-胶束在模拟血液系统中药物输送的流道系统中表现出很高的动态特异性。因此,我们的 DNA 适体-胶束组装在癌细胞识别和体内药物输送应用方面显示出很大的潜力。