Next generation of boron neutron capture therapy (BNCT) agents for cancer treatment

Abstract

Boron neutron capture therapy (BNCT) is one of the most promising treatments among neutron capture therapies due to its long‐term clinical application and unequivocally obtained success during clinical trials. Boron drug and neutron play an equivalent crucial role in BNCT. Nevertheless, current clinically used l‐boronophenylalanine (BPA) and sodium borocaptate (BSH) suffer from large uptake dose and low blood to tumor selectivity, and that initiated overwhelm screening of next generation of BNCT agents. Various boron agents, such as small molecules and macro/nano‐vehicles, have been explored with better success. In this featured article, different types of agents are rationally analyzed and compared, and the feasible targets are shared to present a perspective view for the future of BNCT in cancer treatment. This review aims at summarizing the current knowledge of a variety of boron compounds, reported recently, for the application of BCNT.

Rational Design, Multistep Synthesis and in Vitro Evaluation of Poly(glycerol) Functionalized Nanodiamond Conjugated with Boron‐10 Cluster and Active Targeting Moiety for Boron Neutron Capture Therapy

“…BNCT is attracting much more attentions in recent years since the accelerator-based cancer treatment has obtained regulatory approval in Japan. [4][5][6] In parallel, a lot of works for BNCT drugs with small compounds, macromolecules or nanomaterials have been reported, [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] including poly(glycerol) (PG) functionalized detonation nanodiamonds (DNDs), namely DNDÀ PG, conjugated with 10 B-containing moiety we reported recently. [23] Nanodiamonds (NDs) including DNDs are biologically inert nanoparticles and subjected to various chemical modifications covalently through oxygen containing functional groups on the surface via robust processes.…”

The Dawn of a New Era: Tumor-Targeting Boron Agents for Neutron Capture Therapy

“…51 In the case of BSH, for example, although the high concentration of 10 B contained in this agent can accumulate in tumor regions through the EPR effect, BSH is predominantly located in the interstices of cancer cells owing to the insufficient intracellularization, which restricts its further application. 52 To address the issue, Michiue's team proposed a strategy of connecting BSH with a short arginine peptide (1R, 2R, 3R) and conducted experimental validation (Figure 4, 8). 53 The results showed that the intracellular boron concentration was directly proportional to the peptide content.…”

“…In recent years, peptide ligands have garnered significant attention in the functionalization of carriers, primarily owing to their facile synthesis, low immunogenicity, high affinity for specific targets, and selectivity . In the case of BSH , for example, although the high concentration of 10 B contained in this agent can accumulate in tumor regions through the EPR effect, BSH is predominantly located in the interstices of cancer cells owing to the insufficient intracellularization, which restricts its further application . To address the issue, Michiue’s team proposed a strategy of connecting BSH with a short arginine peptide (1R, 2R, 3R) and conducted experimental validation (Figure , 8 ) .…”

Development of a Gadolinium–Boron-Conjugated Albumin for MRI-Guided Neutron Capture Therapy

“…Sodium mercaptoundecahydro- closo -dodecaborate (BSH), which is a boron cluster containing 12 boron atoms, was used for the treatment of glioma. , l -Boronophenylalanine (BPA) is currently the most-used boron agent in clinical BNCT because it is selectively taken up in tumors through l -type amino acid transporter 1 (LAT1) overexpressed in various cancer cells. ,, Moreover 18 F-labeled BPA-based positron emission tomography (PET) is available to estimate pharmacokinetics of BPA, enabling the prediction of the appropriate timing of neutron irradiation after administration of BPA. , However, it remains challenging to apply BNCT to tumors that express low levels of LAT1. To broaden cancer indications of BNCT, boron agents with different delivery mechanisms from BPA have been developed. − …”