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




Long-circulating DNA lipid nanocapsules as new vector for passive tumor targeting. - Download this document for free, or read online. Document in PDF available to download.

* Corresponding author 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-mPEG2000 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-mPEG2000 10 mm and an early half-life time t1-2 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





Author: Marie Morille - Tristan Montier - Pierre Legras - Nathalie Carmoy - Priscille Brodin - Bruno Pitard - Jean-Pierre Benoît - Cathe

Source: https://hal.archives-ouvertes.fr/



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