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Lipid nanoparticles: tumor-targeting nanocargos for drug and contrast agent delivery

T. Delmas, F. Navarro, J. Gravier, J.S. Thomann, E. Heinrich, J. Mérian, A. Fraichard, R. Boisgard, B. Tavitian, S. Dufort, J.L. Coll, J. Bibette, P. Boisseau, A.C. Couffin, I. Texier
CEA Grenoble, FR

Keywords: lipid nanoparticles, drug delivery, fluorescence imaging, phototherapy


A new technology for the encapsulation of lipophilic molecules -both drugs and contrast agents dedicated to chemotherapy, phototherapy, or fluorescence imaging in oncology- has been developed, based on oil-in-water nanoemulsions. Thorough physico-chemical characterizations of the nanoparticles evidence highly stable (> 1 year) lipid nanoemulsions with amorphous core of temperature- and composition- tuneable viscosity. Moreover, they display low in vitro cytotoxicity (IC50 > 300 µg/mL of lipids for naked particles from 30 to 120 nm diameter), and high tolerance in vivo in single dose study after their systemic injection (rat study, 150 mg/kg dose). Particles can be efficiently loaded with different hydrophobic to amphiphilic molecules, such as fluorescent dyes for tumor labeling, photosensitizers for phototherapy, or chemotoxic drugs. The presence of PEGylated surfactants in the particle coating ensures a good in vivo stealthiness, as assessed by their biodistribution recorded using fluorescence imaging and radioactivity counting (14C and 3H particle labelling). The lipid nanoparticles can moreover be functionalized by tumor-targeting ligands, such as the cRGD peptide exhibiting specific adhesion to αvβ3 integrins expressing cells in vitro (case of 25% of tumor cells). In vivo fluorescence imaging shows an improved tumor accumulation of cRGD-functionalized lipid nanoparticles, compared to the non functionalized ones.
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