Department of Chemistry, University of Miami, Coral Gables, FL 33146, USA.
CESI Engineering School-Angoulême, 16400 La Couronne, France.
Colloids Surf B Biointerfaces. 2019 Apr 1;176:488-493. doi: 10.1016/j.colsurfb.2019.01.031. Epub 2019 Jan 19.
Drug traversal across the blood-brain barrier has come under increasing scrutiny recently, particularly concerning the treatment of sicknesses, such as brain cancer and Alzheimer's disease. Most therapies and medicines are limited due to their inability to cross this barrier, reducing treatment options for maladies affecting the brain. Carbon dots show promise as drug carriers, but they experience the same limitations regarding crossing the blood-brain barrier as many small molecules do. If carbon dots can be prepared from a precursor that can cross the blood-brain barrier, there is a chance that the remaining original precursor molecule can attach to the carbon dot surface and lead the system into the brain. Herein, tryptophan carbon dots were synthesized with the strategy of using tryptophan as an amino acid for crossing the blood-brain barrier via LAT1 transporter-mediated endocytosis. Two types of carbon dots were synthesized using tryptophan and two different nitrogen dopants: urea and 1,2-ethylenediamine. Carbon dots made using these precursors show excitation wavelength-dependent emission, low toxicity, and have been observed inside the central nervous system of zebrafish (Danio rerio). The proposed mechanism for these carbon dots abilities to cross the blood-brain barrier concerns residual tryptophan molecules which attach to the carbon dots surface, enabling them to be recognized by the LAT1 transporter. The role of carbon dots for transport open promising avenues for drug delivery and imaging in the brain.
药物穿越血脑屏障最近受到了越来越多的关注,特别是在治疗脑部疾病方面,如脑癌和老年痴呆症。由于大多数治疗方法和药物无法穿过这一屏障,导致针对影响大脑的疾病的治疗选择有限。碳点作为药物载体显示出了潜力,但它们与许多小分子一样,在穿越血脑屏障方面也存在同样的限制。如果可以从能够穿越血脑屏障的前体中制备碳点,那么前体分子的剩余部分就有可能附着在碳点表面,并将整个系统引导进入大脑。在此,我们采用色氨酸作为氨基酸通过 LAT1 转运体介导的内吞作用来穿越血脑屏障的策略,合成了色氨酸碳点。使用色氨酸和两种不同的氮掺杂剂(尿素和 1,2-乙二胺)合成了两种类型的碳点。这些前体制备的碳点具有激发波长依赖性发射、低毒性的特点,并且已经在斑马鱼(Danio rerio)的中枢神经系统中观察到。这些碳点穿越血脑屏障的能力的提出的机制涉及附着在碳点表面的残留色氨酸分子,使它们能够被 LAT1 转运体识别。碳点在药物输送和脑成像方面的应用为其提供了有前景的途径。