Efficient “green” encapsulation of a highly hydrophilic anticancer drug in metal–organic framework nanoparticles

Abstract

Metal–organic frameworks (MOFs) are coordination polymers of interest for biomedical applications. Of particular importance, nanoparticles made of iron(III) trimesate (MIL-100, MIL standing for Material Institut Lavoisier) (nanoMOFs) can be conveniently synthesised under mild and green conditions. They were shown to be biodegradable, biocompatible and efficient to encapsulate a variety of active molecules. We have addressed here the challenges to encapsulate a highly hydrophilic anticancer prodrug, phosphated gemcitabin (Gem-MP) known for its instability and inability to bypass cell membranes. MIL-100 nanoMOFs acted as efficient “nanosponges”, soaking Gem-MP from its aqueous solution with almost perfect efficiency (>98%). Maximal loadings reached ∼30 wt% reflecting the strong interaction between the drug and the iron trimesate matrices. Neither degradation nor loss of crystalline structure was observed after the loading process. Storage of the loaded nanoMOFs in water did not result in drug release over three days. However, Gem-MP was released in media containing phosphates, as a consequence to particle degradation. Drug-loaded nanoMOFs were effective against pancreatic PANC-1 cells, in contrast to free drug and empty nanoMOFs. However, an efflux phenomenon could contribute to reduce the efficacy of the nanocarriers. Size optimization and surface modification of the nanoMOFs are expected to further improve these findings.

• Gemcitabin
• “green” synthesis
• metal–organic frameworks
• MOF
• nanoparticle
• nucleoside analog
• prostate cancer

Acknowledgements

We are grateful to Salim Hanbli (Institut Galien) for technical assistance during encapsulation studies, to Dr. Hélène Chacun (Institut Galien) for help with the radioactivity measurements and to Dr. Yannis Lazarou (INN, Demokritos) for volume calculations of optimized Gem-MP structures using COSMO (MOPAC), and DFT calculations.

Declaration of interest

The authors have no declarations of interest to report. The authors wish to acknowledge financial support by the European Program FP7-PEOPLE-ITN-2008 “CYCLON”, project #237962 and from the European Program FP7-PEOPLE-ITN-2013 “CycloN Hit”, project #608407.

Supplementary material available online

Supplementary Figures S1 and S2