Nanoscale iron trimesate metal organic framework as potential platform for active nucleoside analogues delivery

V. Agostoni, T. Chalati, P. Horcajada, H. Willaime, P. Couvreur, R. Anand, S. Monti, C. Serre, R. Gref

Keywords: MOF, nanoparticles, NRTI, AZT-TP, drug delivery


The clinical use of active nucleoside reverse transcriptase inhibitors (NRTIs) triphosphate, such as azidothymidine triphosphate (AZT-TP), is limited by their poor stability in biological media and low intracellular uptake. Herein we report the use of a new family of biodegradable nanocarriers for AZT-TP delivery: nanoparticles made of iron trimesate metal organic framework (MIL-100). These coordination polymers have been obtained by hydrothermal synthesis under microwave irradiation taking advantage of the spontaneous coordination between iron trimers and trimesic acid. This “green” technology leads to the formation of biodegradable, non cytotoxic nanoparticles, showing a crystalline micro-mesoporous architecture and a huge adsorption surface. Due to their structure, they act as efficient “nanosponges”, rapidly absorbing, with almost perfect efficiency, important AZT-TP payloads (up to 24wt%), the highest reported so far among biodegradable nanocarriers. An in depth physico-chemical study involving isothermal titration calorimetry, spectroscopic analysis and release studies, established that the strong interaction between AZT-TP and MIL-100’s matrix could be attributed to the presence of phosphate groups, coordinating with the iron sites in the nanoparticles. Contrary to free AZT-TP which does not penetrate inside the cells, nanoencapsulated AZT-TP could be efficiently delivered inside human PBMC, inhibiting up to 90% of the viral replication.