Tryptophan carbon dots and their ability to cross the blood-brain barrier
Tryptophan carbon dots and their ability to cross the blood-brain barrier
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DOI：
10.1016/j.colsurfb.2019.01.031
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发表时间：
2019-04-01
影响因子：
5.8
通讯作者：
Leblanc, Roger M.
中科院分区：
文献类型：
--
作者：
Mintz, Keenan J.;Mercado, Guillaume;Leblanc, Roger M.
最近，药物穿越血脑屏障受到了越来越多的审查，特别是在脑癌和阿尔茨海默病等疾病的治疗方面。由于无法跨越这一障碍，大多数疗法和药物都受到限制，从而减少了影响大脑的疾病的治疗选择。碳点显示出作为药物载体的前景，但它们在跨越血脑屏障方面遇到了与许多小分子相同的限制。如果可以从可以穿过血脑屏障的前体制备碳点，那么剩余的原始前体分子就有可能附着在碳点表面，并将系统引入大脑。利用色氨酸作为一种氨基酸，通过LAT1转运蛋白介导的内吞作用穿过血脑屏障，合成了色氨酸碳点。以色氨酸为原料，尿素和1，2-乙二胺为氮源，合成了两种不同类型的碳点。使用这些前驱体制成的碳点具有激发波长依赖的发射，毒性低，并已在斑马鱼(Dania Retie)的中枢神经系统内观察到。所提出的这些碳点跨越血脑屏障的机制与附着在碳点表面的残存色氨酸分子有关，使它们能够被LAT1转运蛋白识别。碳点在运输中的作用为药物输送和大脑成像开辟了一条很有希望的途径。
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 (Dania retie). 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.