Drug delivery via the transferrin receptor-mediated endocytosis pathway

Abstract

The membrane transferrin receptor-mediated endocytosis has been exploited for developing novel targeted drug delivery systems,which could have a variety of applications in the site-specific delivery of anticancer drugs,proteins and therapeutic genes into proliferating malignant cells that overexpress the transferrin receptors.This is achieved by coupling transferrin or monoclonal antibody to transferrin receptor with therapeutic drugs or drug delivery vesicles.The transferrin conjugates can be obtained by use of either bifunctional chemical linkers or by genetic infusion of therapeutic peptides/proteins into the structure of transferrin /and monoclonal antibody to transferrin receptor.A variety of drug carriers such as liposomes,nanoparticles and DNA-polymer complexes(i.e.polyplex and lipoplex)were used to efficiently deliver the transferrin conjugates.Use of transferrin conjugates results in improvement in drug efficacy,selectivity and drug release as well as reduction in drug toxicity.This paper reviews the basic biochemistry of transferrin and the transferrin receptor as well as the strategy for developing targeted drug delivery system. 膜转铁蛋白受体介导的内吞作用应用于 新的药物靶向给药系统, 包括将抗肿瘤药物, 蛋白和治疗基因定位运输至恶性增殖细胞或是中枢神经系统。通过偶联转铁蛋白或其抗体连接到转铁蛋白受体上成为治疗的药物或转运载体。多种药物载体如脂质 体, 纳米颗粒与DNA复合物用于高效运输治疗物。转铁蛋白复合物的运用不仅提高了药效, 改善了选择性与药物释放性能, 降低了毒性, 同时也延长药物血浆半衰期, 提高药物主动靶性。本篇综述介绍了转铁蛋白/转铁蛋白受体介导的药物运输的研究进展。