Open Access

ARTICLE

In vitro polymerization of the dopamine-borate melanin precursor: A proof-of-concept regarding boron neutron-capture therapy for melanoma

JUAN C. STOCKERT^1,2,*, SILVINA A. ROMERO¹, MARCELO N. FELIX-POZZI³, ALFONSO BLÁZQUEZ-CASTRO⁴

1 Instituto de Oncología “Angel H. Roffo”, Área Investigación, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, C1417DTB, Argentina
2 Centro Integrativo de Biología y Química Aplicada, Universidad Bernardo O’Higgins, Santiago, 8370854, Chile
3 Departamento de Micro y Nanotecnología, Instituto de Nanociencias y Nanotecnología, Centro Atómico Constituyentes, Comisión Nacional de Energía Atómica, Buenos Aires, CP 1650, Argentina
4 Departamento de Biología, Universidad Autónoma de Madrid, Madrid, 28049, Spain

* Corresponding Author: JUAN C. STOCKERT. Email:

BIOCELL 2023, 47(4), 919-928. https://doi.org/10.32604/biocell.2023.026631

Received 17 September 2022; Accepted 26 December 2022; Issue published 08 March 2023

Abstract

The ¹⁰boron neutron-capture therapy (BNCT) is an emerging antitumoral method that shows increasing biomedical interest. BNCT is based on the selective accumulation of the ¹⁰boron isotope within the tumor, which is then irradiated with low-energy thermal neutrons, generating nuclear fission that produces ⁷lithium, ⁴helium, and γ rays. Simple catechol-borate esters have been rather overlooked as precursors of melanin biosynthesis, and therefore, a proof-of-concept approach for using dopamine-borate (DABO) as a suitable boron-containing candidate for potential BNCT is presented here. DABO can spontaneously oxidize and autopolymerize in vitro, giving a soluble, eumelanin-like brown-black poly-DABO product. Melanotic melanoma cell cultures treated with 1 mM DABO for 24 and 48 h were viable and showed no signs of damage or cell death. The stability and possible trans-esterification of DABO is shortly discussed. Chemical calculations and quantitative structure-activity relationships (QSAR) analysis of DABO and the BNCT agent BPA indicated that they should be cell permeant and accumulate within lysosomes and melanosomes. Molecular modeling allows visualization of both the DABO precursor and the structure of a borate derivative of the proposed catechol-porphycene model for eumelanin, showing interesting features from molecular orbital calculations. The main difference between DABO and other agents, such as BPA, is that it is not a boronic acid nor a boron cluster. This simple catechol-borate ester (protected from oxidation and blackening) could be administrated to living cells and organisms, in which biosynthesis of boron-melanin in melanoma melanocytes can lead to improved BNCT.

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