Vitamin B3 metal-organic frameworks as potential delivery vehicles for therapeutic nitric oxide

Publication date: Available online 16 January 2017
Source:Acta Biomaterialia
Author(s): Rosana V. Pinto, Fernando Antunes, João Pires, Vanessa Graça, Paula Brandão, Moisés L. Pinto
The synthesis and structural characterization of two isostructural metal (M=Ni, Co) 3D framework structure that integrate vitamin B3 building blocks with NO delivery capabilities and low toxicity is presented. The compounds with a formula [M2(μ2-H2O)(μ-vitamin B3)4]·2H2O contain two crystallographic distinct divalent metal centers connected by a bridging water and carboxylate group from vitamin B3. The porous compounds have the capability of storing and releasing nitric oxide (NO) in a slow and reversible manner, with released amounts of 2.6 and 2.0 μmol NO mgsolid^-1, on the Ni and Co compound, respectively. The NO release followed a convenient slow release kinetic profile in both gas and liquid phases. Hemoglobin tests demonstrated that NO is released to the medium in a biologically active form, thus suitable to trigger the desired response in biological systems. The toxicity of the samples with and without loaded NO was evaluated from cytotoxicity tests in HeLa and HEKn cells, showing low toxicity of the compounds at concentrations below 180 μg cm^-3. The overall results indicate that these bio based MOFs are of interest for therapeutic applications related with NO delivery.Significance statementThe synthesis and characterization of new vitamin B3 porous metal-organic frameworks (MOFs) is presented in this work for the first time. Few other examples of porous MOFs build up of vitamin exist in the literature with adsorbing capacity like our materials.The ligand (vitamin B3) in these MOFs is much more biocompatible than the usual ligands like, for example, benzene carboxylic acids (terephthalic acid or trimesic acid) and imidazole based ligands.No other vitamin based MOFs have been studied for NO storage.The effects on cell cultures of the materials loaded with NO are studied for the first time and the cell line used is a human primary cell line representative of the human skin. This is relevant for future applications related to wound healing.

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