Early Stage In Vitro Bioprofiling of Potential Low-Molecular-Weight Organoboron Compounds for Boron Neutron Capture Therapy (BNCT)-Proposal for a Guide

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2024 May 24

PMID 38786022

Authors

Zbigniew J Lesnikowski

Filip Ekholm

Narayan S Hosmane

Martin Kellert

Eiji Matsuura

Hiroyuki Nakamura

Agnieszka B Olejniczak

Luigi Panza

Louis M Rendina

Wolfgang A G Sauerwein

Affiliations

Soon will be listed here.

Abstract

Given the renewed interest in boron neutron capture therapy (BNCT) and the intensified search for improved boron carriers, as well as the difficulties of coherently comparing the carriers described so far, it seems necessary to define a basic set of assays and standardized methods to be used in the early stages of boron carrier development in vitro. The selection of assays and corresponding methods is based on the practical experience of the authors and is certainly not exhaustive, but open to discussion. The proposed tests/characteristics: Solubility, lipophilicity, stability, cytotoxicity, and cellular uptake apply to both low molecular weight (up to 500 Da) and high molecular weight (5000 Da and more) boron carriers. However, the specific methods have been selected primarily for low molecular weight boron carriers; in the case of high molecular weight compounds, some of the methods may need to be adapted.

Citing Articles

Towards New Delivery Agents for Boron Neutron Capture Therapy: Synthesis and In Vitro Evaluation of a Set of Fluorinated Carbohydrate Derivatives.

Matovic J, Jarvinen J, Sokka I, Imlimthan S, Aitio O, Sarparanta M Molecules. 2024; 29(17).

PMID: 39275111 PMC: 11397260. DOI: 10.3390/molecules29174263.

References

Oloo S, Smith K, Vicente M . Multi-Functional Boron-Delivery Agents for Boron Neutron Capture Therapy of Cancers. Cancers (Basel). 2023; 15(13). PMC: 10340061. DOI: 10.3390/cancers15133277. View

Sauerwein W, Sancey L, Hey-Hawkins E, Kellert M, Panza L, Imperio D . Theranostics in Boron Neutron Capture Therapy. Life (Basel). 2021; 11(4). PMC: 8070338. DOI: 10.3390/life11040330. View

Justus E, Awad D, Hohnholt M, Schaffran T, Edwards K, Karlsson G . Synthesis, liposomal preparation, and in vitro toxicity of two novel dodecaborate cluster lipids for boron neutron capture therapy. Bioconjug Chem. 2007; 18(4):1287-93. DOI: 10.1021/bc070040t. View

Massari S, Bertagnin C, Pismataro M, Donnadio A, Nannetti G, Felicetti T . Synthesis and characterization of 1,2,4-triazolo[1,5-a]pyrimidine-2-carboxamide-based compounds targeting the PA-PB1 interface of influenza A virus polymerase. Eur J Med Chem. 2020; 209:112944. PMC: 7561591. DOI: 10.1016/j.ejmech.2020.112944. View

Avdeef A . pH-metric log P. II: Refinement of partition coefficients and ionization constants of multiprotic substances. J Pharm Sci. 1993; 82(2):183-90. DOI: 10.1002/jps.2600820214. View

Hattori Y, Andoh T, Kawabata S, Hu N, Michiue H, Nakamura H . Proposal of recommended experimental protocols for in vitro and in vivo evaluation methods of boron agents for neutron capture therapy. J Radiat Res. 2023; 64(6):859-869. PMC: 10665309. DOI: 10.1093/jrr/rrad064. View

Dehring K, Workman H, Miller K, Mandagere A, Poole S . Automated robotic liquid handling/laser-based nephelometry system for high throughput measurement of kinetic aqueous solubility. J Pharm Biomed Anal. 2004; 36(3):447-56. DOI: 10.1016/j.jpba.2004.07.022. View

Raitano A, Martin T, Zhang C, Malinao M, Capo L, Ikeura M . Boronotyrosine, a Borylated Amino Acid Mimetic with Enhanced Solubility, Tumor Boron Delivery, and Retention for the Re-emerging Boron Neutron Capture Therapy Field. J Med Chem. 2023; 66(19):13809-13820. DOI: 10.1021/acs.jmedchem.3c01265. View

Kondo N, Hirano F, Temma T . Evaluation of 3-Borono-l-Phenylalanine as a Water-Soluble Boron Neutron Capture Therapy Agent. Pharmaceutics. 2022; 14(5). PMC: 9143228. DOI: 10.3390/pharmaceutics14051106. View

10.

Patra M, Ingram K, Pierroz V, Ferrari S, Spingler B, Keiser J . Ferrocenyl derivatives of the anthelmintic praziquantel: design, synthesis, and biological evaluation. J Med Chem. 2012; 55(20):8790-8. DOI: 10.1021/jm301077m. View

11.

Balcer E, Giebultowicz J, Sochacka M, Ruszczynska A, Muszynska M, Bulska E . Investigation of the Impact of L-Phenylalanine and L-Tyrosine Pre-Treatment on the Uptake of 4-Borono-L-Phenylalanine in Cancerous and Normal Cells Using an Analytical Approach Based on SC-ICP-MS. Molecules. 2023; 28(18). PMC: 10534874. DOI: 10.3390/molecules28186552. View

12.

Repetto G, Peso A, Zurita J . Neutral red uptake assay for the estimation of cell viability/cytotoxicity. Nat Protoc. 2008; 3(7):1125-31. DOI: 10.1038/nprot.2008.75. View

13.

Bialek-Pietras M, Olejniczak A, Tachikawa S, Nakamura H, Lesnikowski Z . Towards new boron carriers for boron neutron capture therapy: metallacarboranes bearing cobalt, iron and chromium and their cholesterol conjugates. Bioorg Med Chem. 2013; 21(5):1136-42. DOI: 10.1016/j.bmc.2012.12.039. View

14.

Isik M, Levorse D, Rustenburg A, Ndukwe I, Wang H, Wang X . pK measurements for the SAMPL6 prediction challenge for a set of kinase inhibitor-like fragments. J Comput Aided Mol Des. 2018; 32(10):1117-1138. PMC: 6367941. DOI: 10.1007/s10822-018-0168-0. View

15.

Han G, Priefer R . A systematic review of various pK determination techniques. Int J Pharm. 2023; 635:122783. DOI: 10.1016/j.ijpharm.2023.122783. View

16.

Hermans A, Milsmann J, Li H, Jede C, Moir A, Hens B . Challenges and Strategies for Solubility Measurements and Dissolution Method Development for Amorphous Solid Dispersion Formulations. AAPS J. 2022; 25(1):11. DOI: 10.1208/s12248-022-00760-8. View

17.

Ates G, Vanhaecke T, Rogiers V, Rodrigues R . Assaying Cellular Viability Using the Neutral Red Uptake Assay. Methods Mol Biol. 2017; 1601:19-26. DOI: 10.1007/978-1-4939-6960-9_2. View

18.

Manallack D . The pK(a) Distribution of Drugs: Application to Drug Discovery. Perspect Medicin Chem. 2009; 1:25-38. PMC: 2754920. View

19.

Howell N, Middleton R, Sierro F, Fraser B, Wyatt N, Chacon A . Neutron Capture Enhances Dose and Reduces Cancer Cell Viability in and out of Beam During Helium and Carbon Ion Therapy. Int J Radiat Oncol Biol Phys. 2024; 120(1):229-242. DOI: 10.1016/j.ijrobp.2024.02.052. View

20.

Andres A, Roses M, Rafols C, Bosch E, Espinosa S, Segarra V . Setup and validation of shake-flask procedures for the determination of partition coefficients (logD) from low drug amounts. Eur J Pharm Sci. 2015; 76:181-91. DOI: 10.1016/j.ejps.2015.05.008. View