State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
Bioorg Med Chem Lett. 2011 Oct 1;21(19):5982-6. doi: 10.1016/j.bmcl.2011.07.066. Epub 2011 Jul 26.
Transferrin has shown potential in the delivery of anticancer drugs into primarily proliferating malignant cells that over-express transferrin receptors. Constructing transferrin receptor targeted drug delivery system has been widespread concerned. In this study, whether transferrin could transport noncovalent binding drugs into cancer cells has been investigated. Two representative compounds, doxorubicin hydrochloride (Dox) and vanadocene dichloride (Cp(2)VCl(2)), have been chosen to study the interactions with h-Tf and apo-Tf, and the influences in the presence of h-Tf and apo-Tf by using fluorescence spectroscopy, circular dichroism (CD) spectroscopy and MTT assay. The results have shown that both doxorubicin and Cp(2)VCl(2) could bind to h-Tf and apo-Tf but with different binding modes. The results of MTT assay demonstrate that the presence of both h-Tf and apo-Tf has enhanced the antiproliferative activity of Cp(2)VCl(2). However, the anticancer activity of the mixture of doxorubicin and h-Tf is basically the same as that of doxorubicin does. Our studies indicate that transferrin plays an important role in the transport and targeted delivery of Cp(2)VCl(2) into cancer cells.
转铁蛋白在将抗癌药物递送至过度表达转铁蛋白受体的主要增殖恶性细胞中显示出潜力。构建转铁蛋白受体靶向药物传递系统已受到广泛关注。在这项研究中，研究了转铁蛋白是否可以将非共价结合药物转运到癌细胞中。选择了两种代表性化合物，盐酸多柔比星（Dox）和二氯二茂钒（Cp(2)VCl(2)），以研究它们与 h-Tf 和 apo-Tf 的相互作用，以及在存在 h-Tf 和 apo-Tf 时对它们的影响，使用荧光光谱法、圆二色性（CD）光谱法和 MTT 测定法。结果表明，多柔比星和 Cp(2)VCl(2)都可以与 h-Tf 和 apo-Tf 结合，但结合模式不同。MTT 测定结果表明，h-Tf 和 apo-Tf 的存在均增强了 Cp(2)VCl(2)的抗增殖活性。然而，多柔比星和 h-Tf 混合物的抗癌活性与多柔比星基本相同。我们的研究表明，转铁蛋白在将 Cp(2)VCl(2)转运并靶向递送至癌细胞中起着重要作用。
