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.
Highlights
Boron neutron capture therapy (BNCT) is a binary chemoradiotherapeutic approach to cancer treatment that employs boron-containing drugs for the selective killing of tumor cells by the irradiation of low-energy neutrons
The creation of novel sources of epithermal neutrons with improved characteristics together with molecular engineering of new boron delivery agents can lead to the breakthrough in the practical use of the BNCT for the therapy of the tumors, especially those resistant to other treatments (e.g., Taskaev, 2015; Barth et al, 2018; Sato et al, 2018; Taskaev, 2019; Dymova et al, 2020)
An intensive search is still ongoing for possibilities of maximal loading of BNCT agents by the boron-10
Summary
Boron neutron capture therapy (BNCT) is a binary chemoradiotherapeutic approach to cancer treatment that employs boron-containing drugs for the selective killing of tumor cells by the irradiation of low-energy neutrons (epithermal neutrons) (see, e.g., Calabrese et al, 2018). They are considered as perspective high loaded boron carriers for BNCT, antisense/antigene therapeutic agents and tools for molecular diagnostics, electrochemical biosensors, IR-sensitive probes, and modules for nanoconstructs (Schinazi et al, 1994; Lesnikowski, 2003; Olejniczak et al, 2005; ; Lesnikowski, 2007; Ziółkowski et al, 2012; Kwiatkowska et al, 2013; Olejniczak et al, 2013; Kaniowski et al, 2017; Olejniczak et al, 2018; Kaniowski et al, 2020a) In this mini-review, we make a particular focus on the progress in the synthesis of different types of oligonucleotide-based constructs, including antisense DNA oligonucleotides, siRNA, and oligomeric phosphate diesters bearing one or multiple boron clusters in light of the requirements for effective BNCT and future trends in the design of functional nucleic acids and their composites as new potent BNCT agents. Determination of hydrophobicity characteristics (logP or logD values) makes use for estimating the hydrophobicity of oligonucleotide-boron cluster conjugates (Kwiatkowska et al, 2013; Ebenryter-Olbinska et al, 2017)
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