Center for Nanomedicine and Theranostics, Department of Health Technology, Technical University of Denmark, Denmark.
Laboratory for Neurobiology, Biomedicine, Institute of Health Science and Technology, Aalborg University, Aalborg, Denmark.
Prog Neurobiol. 2019 Oct;181:101665. doi: 10.1016/j.pneurobio.2019.101665. Epub 2019 Jul 31.
Obtaining efficient drug delivery to the brain remains the biggest challenge for the development of therapeutics to treat diseases of the central nervous system. The main obstacle is the blood-brain barrier (BBB), which impedes the entrance of most molecules present in the systemic circulation, especially large molecule drugs and nanomedicines. To overcome this obstacle, targeting strategies binding to nutrient receptors present at the luminal membrane of the BBB are frequently employed. Amongst the numerous potential targets at the BBB, the transferrin receptor (TfR) remains the most common target used to ensure sufficient drug delivery to the brain. In this review, we provide a full account on the use of the TfR as a target for brain drug delivery by describing the function of the TfR in the BBB, the historical background of its use in drug delivery, and the most recent evidence suggesting TfR-targeted medicines to be efficient for brain drug delivery with a clear clinical potential.
将药物有效递送至大脑仍然是开发治疗中枢神经系统疾病疗法的最大挑战。主要障碍是血脑屏障 (BBB)，它阻止了大多数存在于全身循环中的分子进入，特别是大分子药物和纳米药物。为了克服这一障碍，经常采用与 BBB 管腔膜上的营养受体结合的靶向策略。在 BBB 上众多潜在的靶标中，转铁蛋白受体 (TfR) 仍然是用于确保将足够的药物递送至大脑的最常用靶标。在这篇综述中，我们通过描述 TfR 在 BBB 中的功能、其在药物递送中的历史背景以及最近的证据，全面阐述了将 TfR 作为脑内药物递送的靶点，这些证据表明 TfR 靶向药物在脑内药物递送方面具有明显的临床潜力。
