Department of Chemistry, Pohang University of Science and Technology, San31, Hyoja-dong, Pohang, Gyungbuk 790-784, South Korea.
Biomaterials. 2011 Mar;32(8):2124-32. doi: 10.1016/j.biomaterials.2010.11.035. Epub 2010 Dec 13.
We have designed a dual-aptamer complex specific to both prostate-specific membrane antigens (PSMA) (+) and (-) prostate cancer cells. In the complex, an A10 RNA aptamer targeting PSMA (+) cells and a DUP-1 peptide aptamer specific to PSMA (-) cells were conjugated through streptavidin. Doxorubicin-loaded onto the stem region of the A10 aptamer was delivered not only to PSMA (+) cells but to PSMA (-) cells, and eventually induced apoptosis in both types of prostate cancer cells. Cell death was monitored by measuring guanine concentration in cells using differential pulse voltammetry (DPV), a simple and rapid electrochemical method, and was further confirmed by directly observing cell morphologies cultured on the transparent indium tin oxide (ITO) glass electrode and checking their viabilities using a trypan blue assay. To investigate the in vivo application of the dual-aptamer system, both A10 and DUP-1 aptamers were immobilized on the surface of thermally cross-linked superparamagnetic iron oxide nanoparticles (TCL-SPION). Selective cell uptakes and effective drug delivery action of these probes were verified by Prussian blue staining and trypan blue staining, respectively.
我们设计了一种双适体复合物，特异性地针对前列腺特异性膜抗原（PSMA）（+）和（-）前列腺癌细胞。在复合物中，通过链霉亲和素将靶向 PSMA（+）细胞的 A10 RNA 适体和特异性靶向 PSMA（-）细胞的 DUP-1 肽适体连接在一起。阿霉素装载到 A10 适体的茎区，不仅递送到 PSMA（+）细胞，也递送到 PSMA（-）细胞，并最终诱导这两种类型的前列腺癌细胞凋亡。通过使用差分脉冲伏安法（DPV）测量细胞中的鸟嘌呤浓度来监测细胞死亡，这是一种简单快速的电化学方法，并通过直接观察在透明氧化铟锡（ITO）玻璃电极上培养的细胞形态并使用台盼蓝测定法检查其活力来进一步证实。为了研究双适体系统的体内应用，将 A10 和 DUP-1 适体都固定在热交联超顺磁性氧化铁纳米颗粒（TCL-SPION）的表面上。通过普鲁士蓝染色和台盼蓝染色分别验证了这些探针的选择性细胞摄取和有效药物传递作用。
