A periodic development of BPA and BSH based derivatives in boron neutron capture therapy (BNCT)

Abstract

A schematic representation of various judicious approaches for the synthesis of BPA and BSH modified compounds for effective BNCT.

Ex Vivo and In Vivo Evaluation of Dodecaborate-Based Clusters Encapsulated in Ferumoxytol Nanoparticles

“…Finally, considering the ability of host–guest interactions to change the properties such as solubility − and given the relevance of boron-rich compounds for boron neutron capture therapy (BNCT), we performed biodistribution experiments in mice to compare free sodium dodecaborate ( 1 ) with sodium dodecaborate encapsulated in ferumoxytol ( 1 @FMX). We find that 1 @FMX localizes in higher concentrations than free 1 at early time points and that the biodistribution and pharmacokinetics of 1 @FMX are similar to those of the BSH anion, a compound previously employed in several BNCT studies. , Overall, this work shows that boron clusters can be efficiently encapsulated into commercial polymer-based nanoparticle carriers, and this encapsulation can lead to altered biodistribution and pharmacokinetic properties in vivo.…”

“…We find that 1@FMX localizes in higher concentrations than free 1 at early time points and that the biodistribution and pharmacokinetics of 1@FMX are similar to those of the BSH anion, a compound previously employed in several BNCT studies. 35,36 Overall, this work shows that boron clusters can be efficiently encapsulated into commercial polymer-based nanoparticle carriers, and this encapsulation can lead to altered biodistribution and pharmacokinetic properties in vivo.…”

Polyglycerol Functionalized 10B Enriched Boron Carbide Nanoparticle as an Effective Bimodal Anticancer Nanosensitizer for Boron Neutron Capture and Photothermal Therapies

“…Under such circumstances, growing numbers of reviews about BNCT has been published for the last few years, reflecting the increasing expectations. [1][2][3][4][5][6][7][8][9][10][11][12] In view of clinical applications, most of the reviews claim the need for novel 10 B carriers to meet the following requirements; 1) low intrinsic toxicity, 2) high boron accumulation in tumor ( 10 B/tumor tissue (wt/wt) ≥ 20 ppm), and 3) rapid clearance from blood and long persistence in tumor ( 10 B concentration ratio in tumor/blood (T/B ratio) ≥ 3). In light of low tumor specificity and retentivity of the two clinically used drugs, sodium borocaptate (BSH) and boronophenylalanine (BPA), [8] the 10 B carriers have been designed toward a nanometer size by conjugating boron agents with (bio)polymers and relatively large molecules, [13][14][15] encapsulating boron agents in micelles, [16,17] and incorporating boron atoms in nanoparticles (NPs).…”

“…[11] In the former two approaches, BSH, BPA and their analogs are mostly used as the boron agents, which may leave some of the problems intrinsic to BSH and BPA unsolved. [9] Although some 10 B carriers gave promising results, BPA-based polymers show a similar cellular uptake mechanism mediated by amino acid transporter (LAT1) to BPA, limiting the kinds of cancer cells Boron neutron capture therapy (BNCT) is a non-invasive cancer treatment with little adverse effect utilizing nuclear fission of 10 B upon neutron irradiation. While neutron source has been developed from a nuclear reactor to a compact accelerator, only two kinds of drugs, boronophenylalanine and sodium borocaptate, have been clinically used for decades despite their low tumor specificity and/or retentivity.…”

“…[ 11 ] In the former two approaches, BSH, BPA and their analogs are mostly used as the boron agents, which may leave some of the problems intrinsic to BSH and BPA unsolved. [ 9 ] Although some 10 B carriers gave promising results, BPA‐based polymers show a similar cellular uptake mechanism mediated by amino acid transporter (LAT1) to BPA, limiting the kinds of cancer cells to which they can apply. [ 13,18 ] Meanwhile, the third approach is simpler in structure based on boron‐containing nanoparticles (NPs).…”