Transfection Ability and Intracellular DNA Pathway of Nanostructured Gene-Delivery Systems

• Published in: Nano letters Vol. 8; no. 8; pp. 2432 - 2436
• Main Authors: Zhang, Xin, Sharma, Kamal Kant, Boeglin, Marcel, Ogier, Joelle, Mainard, Didier, Voegel, Jean-Claude, Mély, Yves, Benkirane-Jessel, Nadia
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01.08.2008
• Subjects: Biological and medical sciences; Biotechnology; Catalytic methods; Condensed matter: structure, mechanical and thermal properties; Cross-disciplinary physics: materials science; rheology; DNA - metabolism; Ethics; Exact sciences and technology; Fundamental and applied biological sciences. Psychology; HeLa Cells; Humans; Intracellular Space - metabolism; Life Sciences; Low-dimensional structures (superlattices, quantum well structures, multilayers): structure, and nonelectronic properties; Materials science; Methods of nanofabrication; Methods. Procedures. Technologies; Nanostructures - chemistry; Others; Physics; Surfaces and interfaces; thin films and whiskers (structure and nonelectronic properties); Transfection - methods; Various methods and equipments; Polyelectrolyte; Cadmium; Multilayers; Biomedical materials; Cyclodextrin; Lysine; DNA; Drug carrier; Nanostructures; Coatings; Medical application
• ISSN: 1530-6984; 1530-6992
• DOI: 10.1021/nl801379y

Considerable efforts have been devoted to the design of structured materials with functional properties. Polyelectrolyte multilayer films are now a well-established nanostructured concept with numerous potential applications, in particular as biomaterial coatings. This technique allows the preparation of nanostructured architectures exhibiting specific properties for cell-activation control and local drug delivery. In this study, we used a multilayered system made of poly-(l-lysine)/hyaluronic acid (PLL/HA) as a reservoir for active DNA complexes with nonviral gene-delivery vectors, PLL, β-cyclodextrin (CD), and PLL-CD. When embedded into the multilayered films, the transfection efficiencies of the DNA complexes and the cell viability were improved. The highest transfection efficiency was obtained with the PLL-CD/plasmid DNA (pDNA) complexes. We found that this high transfection efficiency was related to an efficient internalization of the complexes in the cell cytoplasm and selected nuclei domains through a nonendocytotic pathway. For the first time, we report the intracellular pathway of the pDNA in complexes incorporated into the multilayered system.