New Boron Delivery Agents

Abstract

This proceeding article compiles current research on the development of boron delivery drugs for boron neutron capture therapy that was presented and discussed at the National Cancer Institute (NCI) Workshop on Neutron Capture Therapy that took place on April 20-22, 2022. The most used boron sources are icosahedral boron clusters attached to peptides, proteins (such as albumin), porphyrin derivatives, dendrimers, polymers, and nanoparticles, or encapsulated into liposomes. These boron clusters and/or carriers can be labeled with contrast agents allowing for the use of imaging techniques, such as PET, SPECT, and fluorescence, that enable quantification of tumor-localized boron and their use as theranostic agents.

Keywords: BNCT; albumin; boron cluster; liposome; peptide; porphyrin.

FIG. 1.

Carboranes and metallabis (dicarbollides) on the road to anticancer therapies: From synthesis, characterization, cellular uptake, and in vitro/in vivo biological evaluations to neutron irradiation to defeat cancer.

FIG. 2.

Tumor-selective peptides as highly selective GPCR agonists with meta-carborane derivatives facilitate targeted delivery of high amounts of boron to specific tumor cells. GPCR, G protein-coupled receptor.

FIG. 3.

Design of cRGD-MID-albumin conjugates (A), their ex vivo imaging (B), and BNCT effect in U87MGxenograft model (C). BNCT, boron neutron capture therapy.

FIG. 4.

Molecular structure of a porphyrin-bearing multiple cobaltabis (dicarbollide) groups.

FIG. 5.

Murine biodistribution of boron in BALB/c mice bearing subcutaneous EMT6 tumors, incorporating Na₃[a2-B₂₀H₁₇NH₃] and Na[C₂B₉H₁₁(CH₂)₁₅CH₃] anion species in liposomes, injected dose 349 μg B (17 mg B/kg body weight).

FIG. 6.

(A) Traditional BNCT drug has a 3:1 ratio of BPA in tumor (dark blue) versus normal brain (blue) at L-BPA dose of 250 mg/kg (patients data); (B) proposed nanodrug has a 16:1 ratio of BPA in tumor versus healthy brain with L-BPA at a dose of 50 mg/kg (animal study).

FIG. 7.

MMP inhibitor BNCT agents: 1,4-triazole α-sulfone 1, 1,5-triazole α-sulfone 2, enriched B analog 3, and 1,4-triazole sulfonamide 4.

FIG. 8.

Development of boron-based potential probes and pharmacological agents in the Das group.