Rizvi Sarwat B, Rouhi Sepideh, Taniguchi Shohei, Yang Shi Yu, Green Mark, Keshtgar Mo, Seifalian Alexander M
UCL Centre for Nanotechnology and Regenerative Medicine, University College London, London, UK.
Department of Physics, King's College London, London, UK.
Int J Nanomedicine. 2014 Mar 11;9:1323-37. doi: 10.2147/IJN.S51535. eCollection 2014.
Quantum dots are fluorescent nanoparticles with unique photophysical properties that allow them to be used as diagnostic, therapeutic, and theranostic agents, particularly in medical and surgical oncology. Near-infrared-emitting quantum dots can be visualized in deep tissues because the biological window is transparent to these wavelengths. Their small sizes and free surface reactive groups that can be conjugated to biomolecules make them ideal probes for in vivo cancer localization, targeted chemotherapy, and image-guided cancer surgery. The human epidermal growth factor receptor 2 gene (HER2/neu) is overexpressed in 25%-30% of breast cancers. The current methods of detection for HER2 status, including immunohistochemistry and fluorescence in situ hybridization, are used ex vivo and cannot be used in vivo. In this paper, we demonstrate the application of near-infrared-emitting quantum dots for HER2 localization in fixed and live cancer cells as a first step prior to their in vivo application.
Near-infrared-emitting quantum dots were characterized and their in vitro toxicity was established using three cancer cell lines, ie, HepG2, SK-BR-3 (HER2-overexpressing), and MCF7 (HER2-underexpressing). Mouse antihuman anti-HER2 monoclonal antibody was conjugated to the near-infrared-emitting quantum dots.
In vitro toxicity studies showed biocompatibility of SK-BR-3 and MCF7 cell lines with near-infrared-emitting quantum dots at a concentration of 60 μg/mL after one hour and 24 hours of exposure. Near-infrared-emitting quantum dot antiHER2-antibody bioconjugates successfully localized HER2 receptors on SK-BR-3 cells.
Near-infrared-emitting quantum dot bioconjugates can be used for rapid localization of HER2 receptors and can potentially be used for targeted therapy as well as image-guided surgery.
量子点是具有独特光物理性质的荧光纳米颗粒,使其能够用作诊断、治疗和诊疗试剂,特别是在医学和外科肿瘤学领域。发射近红外光的量子点能够在深部组织中被可视化,因为生物窗口对这些波长是透明的。它们的小尺寸以及可与生物分子共轭的自由表面反应基团使其成为体内癌症定位、靶向化疗和图像引导癌症手术的理想探针。人表皮生长因子受体2基因(HER2/neu)在25%-30%的乳腺癌中过表达。目前检测HER2状态的方法,包括免疫组织化学和荧光原位杂交,都是离体使用的,不能用于体内。在本文中,我们展示了发射近红外光的量子点在固定和活癌细胞中用于HER2定位的应用,作为其体内应用的第一步。
对发射近红外光的量子点进行了表征,并使用三种癌细胞系,即HepG2、SK-BR-3(HER2过表达)和MCF7(HER2低表达)确定了其体外毒性。将小鼠抗人抗HER2单克隆抗体与发射近红外光的量子点共轭。
体外毒性研究表明,在暴露1小时和24小时后,SK-BR-3和MCF7细胞系与浓度为60μg/mL的发射近红外光的量子点具有生物相容性。发射近红外光的量子点抗HER2抗体生物共轭物成功地将HER2受体定位在SK-BR-3细胞上。
发射近红外光的量子点生物共轭物可用于快速定位HER2受体,并有可能用于靶向治疗以及图像引导手术。