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Transferrin/transferrin receptor-mediated drug delivery.
Medicinal Research Reviews ( IF 13.3 ) Pub Date : 2002-04-05 , DOI: 10.1002/med.10008
Hongyan Li 1 , Zhong Ming Qian
Affiliation  

Since transferrin was discovered more than half a century ago, a considerable effort has been made towards understanding tranferrin-mediated iron uptake. However, it was not until recently with the identification and characterization of several new genes related to iron homeostasis, such as the hemochromatosis protein HFE and the iron transporter DMT1, that our knowledge has been advanced dramatically. A major pathway for cellular iron uptake is through internalization of the complex of iron-bound transferrin and the transferrin receptor, which is negatively modulated by HFE, a protein related to hereditary hemochromatosis. Iron is released from transferrin as the result of the acidic pH in endosome and then is transported to the cytosol by DMT1. The iron is then utilized as a cofactor by heme and ribonucleotide reductase or stored in ferritin. Apart from iron, many other metal ions of therapeutic and diagnostic interests can also bind to transferrin at the iron sites and their transferrin complexes can be recognized by many cells. Therefore, transferrin has been thought as a "delivery system" for many beneficial and harmful metal ions into the cells. Transferrin has also be widely applied as a targeting ligand in the active targeting of anticancer agents, proteins, and genes to primary proliferating malignant cells that overexpress transferrin receptors. This is achieved by conjugation of transferrin with drugs, proteins, hybride systems with marcomolecules and as liposomal-coated systems. Conjugates of anticancer drugs with transferrin can significantly improve the selectivity and toxicity and overcome drug resistance, thereby leading to a better treatment. The coupling of DNA to transferrin via a polycation such as polylysine or via cationic liposomes can target and transfer of the extrogenous DNA particularly into proliferating cells through receptor-mediated endocytosis. These kinds of non-viral vectors are potential alternatives to viral vectors for gene therapy, if the transfection efficiency can be improved. Moreover, transferrin receptors have shown potentials in delivery of therapeutic drugs or genes into the brain across blood-brain barrier.

中文翻译:

转铁蛋白/转铁蛋白受体介导的药物递送。

自从半个多世纪前发现转铁蛋白以来,人们在理解转铁蛋白介导的铁吸收方面做出了相当大的努力。但是,直到最近才鉴定和鉴定了与铁稳态相关的几个新基因,例如血色素沉着病蛋白HFE和铁转运蛋白DMT1,才使我们的知识得到了极大的发展。细胞摄取铁的主要途径是通过铁结合的转铁蛋白和转铁蛋白受体的复合物的内在化,而这种复合物受HFE(与遗传性血色素沉着症有关的蛋白质)的负调控。由于内体中的酸性pH,铁从运铁蛋白中释放出来,然后通过DMT1转运到细胞质中。然后,铁被血红素和核糖核苷酸还原酶用作辅因子,或存储在铁蛋白中。除铁外,许多其他具有治疗和诊断意义的金属离子也可以在铁位点结合运铁蛋白,并且它们的运铁蛋白复合物可以被许多细胞识别。因此,转铁蛋白已被认为是许多有益和有害金属离子进入细胞的“传递系统”。转铁蛋白也已广泛用作靶向配体,用于将抗癌药,蛋白质和基因主动靶向过表达转铁蛋白受体的原代增殖性恶性细胞。这是通过将转铁蛋白与药物,蛋白质,具有马分子的杂交系统以及脂质体包被的系统缀合来实现的。抗癌药物与转铁蛋白的结合可以显着提高选择性和毒性,克服耐药性,从而导致更好的治疗。DNA通过聚阳离子如赖氨酸或通过阳离子脂质体与运铁蛋白的偶联可以靶向外源DNA并通过受体介导的内吞作用转移到增殖细胞中。如果可以提高转染效率,则这些类型的非病毒载体是用于基因治疗的病毒载体的潜在替代品。此外,转铁蛋白受体已显示出将治疗药物或基因穿过血脑屏障输送到大脑的潜力。
更新日期:2019-11-01
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