nanoMIL100: a novel efficient tool to target lung cancer

Lung cancer (LC) is a major health problem, accounting for near 27% of all cancer deaths. Each year, more people die of LC than colon, breast, and prostate cancers combined (1). This fact evidences the urgent need to improve... [ view full abstract ]

Lung cancer (LC) is a major health problem, accounting for near 27% of all cancer deaths. Each year, more people die of LC than colon, breast, and prostate cancers combined (1). This fact evidences the urgent need to improve current available therapy. To increase LC therapy and to reduce its toxicity we propose the use of MOF-based nanoparticles (NP). In particular, we have developed a formulation that passively targets the lungs without any visible signs of toxicity based on MIL-100(Fe), a mesoporous iron(III) trimesate MOF.
NP were prepared and characterized as described elsewhere (2). To evaluate their in vivo biodistribution and toxicity at early times (up to 24 h), a first study was performed in Sprague-Dawley rats. An important accumulation of the NP was observed in the lungs by measuring the iron concentration by atomic absorption spectroscopy. In accordance with our previous data, animals did not present any signs of toxicity. This result encouraged the evaluation of the impact of the loading of Gemcitabine-monophosphate (GMP), a well-known drug used in LC treatment, into MIL100 NP, on drug organ accumulation.
Tritiated-GMP was encapsulated by the impregnation method as previously described (3). C57BL/6JRj mice were treated iv with 10 mg/kg of the free drug and the equivalent dose of MIL100 encapsulated drug. When administered in NP, GMP concentration in lungs was five-fold higher than free GMP after 15 min and remained three-fold larger after 8h (Figure 1).

Thus, MIL100 NP appear as an efficient tool to target the lungs to treat pulmonary diseases.
1. American Cancer Society statistics (last revised 2015).
2. P. Horcajada et al. Chem. Rev., 2012, 112(2) 1232.
3. V. Rodriguez-Ruis et al. J Drug Target. 2015, 23(7-8), 759.

Figure 1 Drug accumulation (measured as disintegrations per second per mg of organ).