Department of Chemistry and Department of Physiology and Functional Genomics, Shands Cancer Center and Center for Research at the Bio/Nano Interface, University of Florida, Gainesville, Florida, United States of America.
PLoS One. 2012;7(4):e33434. doi: 10.1371/journal.pone.0033434. Epub 2012 Apr 25.
Using antibody/aptamer-drug conjugates can be a promising method for decreasing toxicity, while increasing the efficiency of chemotherapy.
METHODOLOGY/PRINCIPAL FINDINGS: In this study, the antitumor agent Doxorubicin (Dox) was incorporated into the modified DNA aptamer TLS11a-GC, which specifically targets LH86, a human hepatocellular carcinoma cell line. Cell viability tests demonstrated that the TLS11a-GC-Dox conjugates exhibited both potency and target specificity. Importantly, intercalating Dox into the modified aptamer inhibited nonspecific uptake of membrane-permeable Dox to the non-target cell line. Since the conjugates are selective for cells that express higher amounts of target proteins, both criteria noted above are met, making TLS11a-GC-Dox conjugates potential candidates for targeted delivery to liver cancer cells.
CONCLUSIONS/SIGNIFICANCE: Considering the large number of available aptamers that have specific targets for a wide variety of cancer cells, this novel aptamer-drug intercalation method will have promising implications for chemotherapeutics in general.
使用抗体/适体-药物偶联物是降低毒性、提高化疗效率的一种很有前途的方法。
方法/主要发现：在这项研究中，将抗肿瘤药物阿霉素（Dox）与专门针对 LH86（一种人肝癌细胞系）的改良 DNA 适体 TLS11a-GC 结合。细胞活力测试表明，TLS11a-GC-Dox 缀合物具有效力和靶向特异性。重要的是，将阿霉素插入修饰的适体中抑制了膜通透性 Dox 对非靶细胞系的非特异性摄取。由于缀合物对表达更高靶蛋白量的细胞具有选择性，因此满足了上述两个标准，这使得 TLS11a-GC-Dox 缀合物成为肝癌细胞靶向递药的潜在候选物。
结论/意义：考虑到有大量针对各种癌细胞的特异性适体，这种新的适体-药物插入方法将为化疗药物的发展带来广阔的前景。
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