Efficient “green” technology to load an anticancer drug, gemcitabine monophosphate, into Iron-Trimesate MOF nanoparticles

V.R. Ruiz, V. Agostoni, H. Willaime, P. Horcajada, C. Serre, M. Lampropoulou, K. Yanakopoulous, R. Gref
Université Paris-Sud, FR

Keywords: gemcitabine monophosphate, anticancer drug, nanoparticle, metal organic framework, controlled release


We have developed new, stable nanocarriers which allow the efficiently entrapment of challenging anticancer drugs such as gemcitabine monophosphate (dFdC-MP). Gemcitabine (dFdC) must be phosphorylated inside the cells to its triphosphate (dFdC-TP) active form. Since the first phosphorylation step is rate limiting, this problem could be addressed by the direct administration of Gemcitabine monophosphate (dFdC-MP). Nanoscale Iron-Trimesate metal organic framework (nanoMOFs) have been chosen as a drug delivery system to overcome dFdC limitations such as (i) its fast deamination (ii) its high hydrophilicity that prevents its diffusion through cell membranes and (iii) its lack of targeting towards neoplasic cells. The aim of the research was to encapsulate dFdC-MP into nanoMOFs in order to (i) protect the anticancer agent (ii) allow its penetration into cells and (iii) control release inside cells. Results confirm that nanoMOFs are excellent drug-delivery nanocarriers allowing a rapid entrapment of dFdC-MP with a high loading efficiency. Release studies have also shown that dFdC-MP release was mediated by the concentration of phosphates in the media. Moreover, HPLC results shown that dFdC-MP is released intact. These results open new perspectives for the administration of active dFdC-MP which might improve its efficacy together with decreasing the administered doses.