Final Report Summary - BIOMOFS (Bioapplications of Metal Organic Frameworks)
The BioMOFs project consisted of exploring from both experimental and modelling standpoints, the encapsulation and release of bioactive molecules including model or challenging drugs, cosmetics and biological gases from porous crystalline hybrid also denoted MOFs for Metal Organic Frameworks.
During the first part of the project (2.5 years), various functionalised MOFs based on non toxic metals (Fe, Ti, Zr) and linkers (endogenous or exogenous polycarboxylic acids) were first prepared at the microparticle size, prior to their use for the encapsulation of several model drugs in order to understand the host-guest interactions. Another possibility to control the release of drugs was to directly couple the therapeutic molecule (bearing several complexing groups) to a biocompatible cation, building up a MOF (Bio-MIL) within which the linker is the active compound. First adsorption and release tests of biological gases through the chemisorption of nitric oxide on the Lewis unsaturated metal sites of a few selected MOFs, were also conducted (coll. St Andrews, UK).
In parallel, nanoparticles of several porous iron(III) carboxylate MOFs were synthesized by solvothermal microwave assisted synthesis, and further used for the encapsulation and controlled release of higher interest drugs (antitumoral, antiretroviral, antiviral). Very large loading capacities, far exceeding those of other carriers, as well as their controlled release were achieved. In addition to their imaging properties, absence of toxicity was evidenced for high doses of these iron carboxylates nanoparticles administered intravenously to rats. Noteworthy, a first biodistribution study revealed that after the biodegradation of these iron carboxylates nanoparticles, excess of iron and non-metabolized exogenous linkers are excreted through urines and faeces after their intravenous administration.
Finally, in addition to the DFT study of the model drug-MOFs interactions, a few QSPR models (QSAR for quantitative structure-property relationships), based on experimental drug loading and/or MOF degradability, were developed in order to build up a predictive model that will be used later to choose the best MOF for a given biomolecule and bioapplication.
During the first part of the project (2.5 years), various functionalised MOFs based on non toxic metals (Fe, Ti, Zr) and linkers (endogenous or exogenous polycarboxylic acids) were first prepared at the microparticle size, prior to their use for the encapsulation of several model drugs in order to understand the host-guest interactions. Another possibility to control the release of drugs was to directly couple the therapeutic molecule (bearing several complexing groups) to a biocompatible cation, building up a MOF (Bio-MIL) within which the linker is the active compound. First adsorption and release tests of biological gases through the chemisorption of nitric oxide on the Lewis unsaturated metal sites of a few selected MOFs, were also conducted (coll. St Andrews, UK).
In parallel, nanoparticles of several porous iron(III) carboxylate MOFs were synthesized by solvothermal microwave assisted synthesis, and further used for the encapsulation and controlled release of higher interest drugs (antitumoral, antiretroviral, antiviral). Very large loading capacities, far exceeding those of other carriers, as well as their controlled release were achieved. In addition to their imaging properties, absence of toxicity was evidenced for high doses of these iron carboxylates nanoparticles administered intravenously to rats. Noteworthy, a first biodistribution study revealed that after the biodegradation of these iron carboxylates nanoparticles, excess of iron and non-metabolized exogenous linkers are excreted through urines and faeces after their intravenous administration.
Finally, in addition to the DFT study of the model drug-MOFs interactions, a few QSPR models (QSAR for quantitative structure-property relationships), based on experimental drug loading and/or MOF degradability, were developed in order to build up a predictive model that will be used later to choose the best MOF for a given biomolecule and bioapplication.