Järvinen Juulia, Pulkkinen Herkko, Rautio Jarkko, Timonen Juri M
School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, 70211 Kuopio, Finland.
Department of Technical Physics, Faculty of Science, Forestry and Technology, University of Eastern Finland, 70211 Kuopio, Finland.
Pharmaceutics. 2023 Nov 23;15(12):2663. doi: 10.3390/pharmaceutics15122663.
Interest in the design of boronated amino acids has emerged, partly due to the utilization of boronophenylalanine (BPA), one of the two agents employed in clinical Boron Neutron Capture Therapy (BNCT). The boronated amino acids synthesized thus far for BNCT investigations can be classified into two categories based on the source of boron: boronic acids or carboranes. Amino acid-based boron carriers, employed in the context of BNCT treatment, demonstrate significant potential in the treatment of challenging tumors, such as those located in the brain. This review aims to shed light on the developmental journey and challenges encountered over the years in the field of amino acid-based boron delivery compound development. The primary focus centers on the utilization of the large amino acid transporter 1 (LAT1) as a target for boron carriers in BNCT. The development of efficient carriers remains a critical objective, addressing challenges related to tumor specificity, effective boron delivery, and rapid clearance from normal tissue and blood. LAT1 presents an intriguing and promising target for boron delivery, given its numerous characteristics that make it well suited for drug delivery into tumor tissues, particularly in the case of brain tumors.
对硼化氨基酸设计的兴趣已经出现，部分原因是硼中子俘获疗法（BNCT）临床应用中使用的两种药物之一——硼代苯丙氨酸（BPA）。迄今为止，为BNCT研究合成的硼化氨基酸根据硼的来源可分为两类：硼酸或碳硼烷。在BNCT治疗中使用的基于氨基酸的硼载体在治疗具有挑战性的肿瘤（如位于脑部的肿瘤）方面显示出巨大潜力。本综述旨在阐明多年来在基于氨基酸的硼递送化合物开发领域所经历的发展历程和遇到的挑战。主要重点集中在利用大中性氨基酸转运体1（LAT1）作为BNCT中硼载体的靶点。开发高效载体仍然是一个关键目标，要应对与肿瘤特异性、有效的硼递送以及从正常组织和血液中快速清除相关的挑战。鉴于LAT1具有众多使其非常适合将药物递送至肿瘤组织（特别是脑肿瘤）的特性，它是硼递送的一个有趣且有前景的靶点。
