Recent Advances in the Synthesis of High Boron-Loaded Nucleic Acids for BNCT

Abstract

Boron clusters attract considerable attention as promising therapeutic tools for boron neutron capture therapy (BNCT). They combine high boron content with high chemical and biological stability, biorthogonality, and low toxicity. The development of oligonucleotide-based constructs and nucleic acid-like molecules, such as oligomeric phosphate diesters, bearing one or multiple boron clusters permits to create potential high boron-loaded agents for BNCT with good bioavailability, specifically interacting with nucleic acids inside the cell. Here, we shortly review the strategies and solutions in the design of oligonucleotide conjugates with boron clusters in light of the requirements for effective BNCT and future prospects of their practical use.

Keywords: BNCT; boron cluster; boron neutron capture therapy; conjugation method; oligonucleotide conjugate; pre- and post-synthetic modification.

FIGURE 1

(A) Boron clusters applied in the engineering of biologically active boron-modified compounds (B) Monomeric synthons and polymer support for the solid-phase synthesis of oligonucleotides bearing boron clusters (C) Post-synthetic approaches for the incorporation of boron clusters into oligonucleotides.

FIGURE 2

The examples of conjugates of nucleic acids and NA-like oligomeric phosphate diesters with boron clusters.