Amino Acid-Based Boron Carriers in Boron Neutron Capture Therapy (BNCT)

Abstract

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.

Metallacarboranes in Medicinal Chemistry: Current Advances and Future Perspectives

“…Unfortunately, presented compounds still fail to fulfill all of the requirements listed for the ideal boron carrier in the BNCT treatment: they have insufficient cellular uptake and poor selectivity for cancerous over healthy cells, thus the search for novel and improved compounds still continues. At the very forefront of this hunt are various derivatives of carborane (C 2 B 10 H 12 ) and dodecaborate ([B 12 H 12 ] 2– ) molecules described in detail in many recent reviews − and books. − As rich boron atoms’ sources these 12-vertex boron cages are often attached to other molecules creating boronated polyamines, − amino acids, nucleic acids and nucleosides, carbohydrates, porphyrins, − phthalocyanines, , liposomes, , dendrimers, − and nanotubes . However, other auspicious candidates for bridging this gap are metallacarboranes (with [COSAN] − in particular), which possess a few characteristics (described in detail in the next chapters) underlying their utility as the 10 B source for neutron irradiation such as ability to cross cellular membranes without their disruption, accumulation inside nucleus and no apparent cytotoxicity.…”