Abstracts Book - IMRC 2018

• SC7-P006
NANOMETRIC MIL-125-NH2 METAL-ORGANIC FRAMEWORK AS
NERVE AGENT ANTIDOTE CARRIER
Sérgio M.f. Vilela 1 , Pablo Salcedo Abraira 1 , Isabelle Colinet 2 , Fabrice Salles 3 , Martijn C. de
Koning 4 , Marloes J.a. Joosen 5 , Christian Serre 2,6 , Patricia Horcajada 1
1 IMDEA Energy, Advanced Porous Materials Unit, Spain. 2 CNRS, Institut Lavoisier de Versailles,
France. 3 CNRS, Institut Charles Gerhardt Montpellier, France. 4 TNO, TNO, Netherlands. 5 TNO, ,
Netherlands. 6 CNRS, Institut des Matériaux Poreux de Paris, France.
Organophosphate pesticides (OP; also used as chemical warfare agents) are one
of the top causes of poisoning worldwide. OP poisoning therapy entails the
administration of “oximes”, able to restore the neuronal activity. Pralidoxime (2-
pyridinium aldoxime methyl chloride or 2-PAM) is a highly active oxime.
However, its permanent positive charge hinders its blood brain barrier (BBB)
penetration, limiting its action at central nervous sites. Nanoscaled Metal-
Organic Frameworks (nanoMOFs) has emerged as promising drug nanocarriers
due to their biocompatibility, high drug loading and controlled release.
Thus, we have pioneering proposed the 3D microporous titanium
aminoterephthalate MIL-125-NH 2 as drug nanocarrier. First, MIL-125-NH 2 ,
exhibiting both a high porosity (associated with important payloads) and
photoactive properties (acting as potential catalyst in the OP photodegradation),
was successfully prepared as monodispersed nanoparticles compatible with
intravenous administration. The obtained MIL-125-NH2 NPs were fully
characterized (PXRD, FTIR, TGA, SEM, Ar sorption measurements and colloidal
stability under relevant physiological conditions). Thus, these colloidally stable
solutions 2-PAM were able to effectively encapsulate the 2-PAM into the MIL-
125-NH 2 porosity. 2-PAM interacted with the pore walls via π-stacking and
hydrogen bonds, as deduced FTIR and Monte Carlo simulation studies. Finally,
2-PAM was rapidly released MIL-125-NH 2 under in vitro conditions. However,
one could expect a more progressive drug delivery under in vivo conditions due
to the formation of a protein corona, as suggested by our surface studies.
Acknowledgment:
This work was partially supported by the CNRS, Université de Versailles, IMDEA
Energy Institute and EU funding through the ERC-2007-209241-BioMOFs ERC.
PH acknowledges the Spanish Ramon y Cajal Programme (grant agreement n