L-Type amino acid transporter 1 as a target for drug delivery

被引:120
作者
Puris, Elena [1 ,2 ]
Gynther, Mikko [1 ]
Auriola, Seppo [1 ]
Huttunen, Kristiina M. [1 ]
机构
[1] Univ Eastern Finland, Sch Pharm, POB 1627, FI-70211 Kuopio, Finland
[2] Ruprecht Karls Univ Heidelberg, Inst Pharm & Mol Biotechnol, D-69120 Heidelberg, Germany
基金
芬兰科学院;
关键词
drug delivery systems; L-type amino acid transporter 1; membrane transporter; targeting; BLOOD-BRAIN-BARRIER; NEUTRON-CAPTURE THERAPY; CARRIER-MEDIATED TRANSPORT; L-LEUCINE TRANSPORT; L-DOPA; UTILIZING PRODRUGS; LAT1; EXPRESSION; ESTER PRODRUGS; VALPROIC ACID; CANCER;
D O I
10.1007/s11095-020-02826-8
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Our growing understanding of membrane transporters and their substrate specificity has opened a new avenue in the field of targeted drug delivery. The L-type amino acid transporter 1 (LAT1) has been one of the most extensively investigated transporters for delivering drugs across biological barriers. The transporter is predominantly expressed in cerebral cortex, blood-brain barrier, blood-retina barrier, testis, placenta, bone marrow and several types of cancer. Its physiological function is to mediate Na+ and pH independent exchange of essential amino acids: leucine, phenylalanine, etc. Several drugs and prodrugs designed as LAT1 substrates have been developed to improve targeted delivery into the brain and cancer cells. Thus, the anti-parkinsonian drug, L-Dopa, the anti-cancer drug, melphalan and the anti-epileptic drug gabapentin, all used in clinical practice, utilize LAT1 to reach their target site. These examples provide supporting evidence for the utility of the LAT1-mediated targeted delivery of the (pro)drug. This review comprehensively summarizes recent advances in LAT1-mediated targeted drug delivery. In addition, the use of LAT1 is critically evaluated and limitations of the approach are discussed.
引用
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页数:17
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