Long-circulating DNA lipid nanocapsules as new vector for passive tumor targeting.

Marie Morille 1 Tristan Montier 2 Pierre Legras 3 Nathalie Carmoy 2 Priscille Brodin 4 Bruno Pitard 5 Jean-Pierre Benoît 1 Catherine Passirani 1, *
* Auteur correspondant
1 Ingénierie de la vectorisation particulaire
2 Génétique moléculaire et génétique épidémiologique
3 SCAHU - Service Commun Animalerie hospitalo-universitaire
4 Institut Pasteur de Corée
5 Institut du thorax
Abstract : Systemic gene delivery systems are needed for therapeutic application to organs that are inaccessible by percutaneous injection. Currently, the main objective is the development of a stable and non-toxic vector that can encapsulate and deliver foreign genetic material to target cells. To this end, DNA, complexed with cationic lipids i.e. DOTAP/DOPE, was encapsulated into lipid nanocapsules (LNCs) leading to the formation of stable nanocarriers (DNA LNCs) with a size inferior to 130 nm. Amphiphilic and flexible poly (ethylene glycol) (PEG) polymer coatings [PEG lipid derivative (DSPE-mPEG(2000)) or F108 poloxamer] at different concentrations were selected to make DNA LNCs stealthy. Some of these coated lipid nanocapsules were able to inhibit complement activation and were not phagocytized in vitro by macrophagic THP-1 cells whereas uncoated DNA LNCs accumulated in the vacuolar compartment of THP-1 cells. These results correlated with a significant increase of in vivo circulation time in mice especially for DSPE-mPEG(2000) 10 mm and an early half-life time (t(1/2) of distribution) 5-fold greater than for non-coated DNA LNCs (7.1 h vs 1.4 h). Finally, a tumor accumulation assessed by in vivo fluorescence imaging system was evidenced for these coated LNCs as a passive targeting without causing any hepatic damage.
Keywords : blood circulation EPR effect non-viral vector stealth properties tumor accumulation poly (ethylene glycol)
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Article dans une revue
Biomaterials, Elsevier, 2010, 31 (2), pp.321-9. 〈10.1016/j.biomaterials.2009.09.044〉
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Marie Morille, Tristan Montier, Pierre Legras, Nathalie Carmoy, Priscille Brodin, et al.. Long-circulating DNA lipid nanocapsules as new vector for passive tumor targeting.. Biomaterials, Elsevier, 2010, 31 (2), pp.321-9. 〈10.1016/j.biomaterials.2009.09.044〉. 〈inserm-00491402〉

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