Adenoviral Gene Delivery from Multilayered Polyelectrolyte Architectures

Authors


  • M.D. gratefully acknowledges Bernard Senger, Dominique Vautier, Nadia Jessel, and Vincent Ball for helpful discussions, Cosette Betscha, Aurore Schneider, and Gregory Francius for help with QCM experiments, Erell Le Guen for providing PLLFITC, Jean-Daniel Abraham for AdGFP construction, Marie Parnot for help with cell culture, Sylvie Schmidt for macrophages, Cathy Royer for hepatocytes preparation, Christine Thumann for help with Facscan experiments, and the Faculté de Chirurgie Dentaire de Strasbourg and the Cancéropole Grand Est-ACI 2004 for financial support.

Abstract

The alternate layer-by-layer (LBL) deposition of polycations and polyanions for the build up of multilayered polyelectrolyte films is an original approach that allows the preparation of tunable, biologically active surfaces. The resulting supramolecular nanoarchitectures can be functionalized with drugs, peptides, and proteins, or DNA molecules that are able to transfect cells in vitro. We monitor, for the first time, the embedding of a bioactive adenoviral (Ad) vector in multilayered polyelectrolyte films. Ad efficiently adsorbs on poly(L-lysine)–poly(L-glutamic acid) (PLL–PGA), PLL–HA (HA: hyaluronan), poly(allylamin hydrochloride)–poly(sodium-4-styrenesulfonate) (PAH–PSS), and CHI–HA (CHI: chitosan) films; it preserves its transduction capacity (which can reach 95 %) for a large number of cell types, and also allows vector uptake into receptor-deficient cells, thus abrogating the restricted tropism of Ad.

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