title: Ligand-Modified Human Serum Albumin Nanoparticles for Enhanced Gene Delivery.
abstract: The development of nonviral gene delivery systems is a great challenge to enable safe gene therapy. In this study, ligand-modified nanoparticles based on human serum albumin (HSA) were developed and optimized for an efficient gene therapy. Different glutaraldehyde cross-linking degrees were investigated to optimize the HSA nanoparticles for gene delivery. The peptide sequence arginine-glycine-aspartate (RGD) and the HIV-1 transactivator of transduction sequence (Tat) are well-known as promising targeting ligands. Plasmid DNA loaded HSA nanoparticles were covalently modified on their surface with these different ligands. The transfection potential of the obtained plasmid DNA loaded RGD- and Tat-modified nanoparticles was investigated in vitro, and optimal incubation conditions for these preparations were studied. It turned out that Tat-modified HSA nanoparticles with the lowest cross-linking degree of 20% showed the highest transfection potential. Taken together, ligand-functionalized HSA nanoparticles represent promising tools for efficient and safe gene therapy.
authors.affiliation: Institute of Pharmaceutical Technology and Biopharmacy, University of Muenster , Corrensstraße 48, Muenster 48149, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Look
authors.affiliation: Fraunhofer Institute for Biomedical Engineering , Joseph-von-Fraunhofer-Weg 1, 66280 Sulzbach, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Wilhelm
authors.affiliation: Fraunhofer Institute for Biomedical Engineering , Joseph-von-Fraunhofer-Weg 1, 66280 Sulzbach, Germany.
authors.forename: Hagen
authors.initials: H
authors.lastname: von Briesen
authors.affiliation: apceth GmbH & Co. KG , Max-Lebsche-Platz 30, 81377 Munich, Germany.
authors.forename: Nadja
authors.initials: N
authors.lastname: Noske
authors.affiliation: apceth GmbH & Co. KG , Max-Lebsche-Platz 30, 81377 Munich, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Günther
authors.affiliation: Institute of Pharmaceutical Technology and Biopharmacy, University of Muenster , Corrensstraße 48, Muenster 48149, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Langer
authors.affiliation: Fraunhofer Institute for Biomedical Engineering , Joseph-von-Fraunhofer-Weg 1, 66280 Sulzbach, Germany.
authors.forename: Erwin
authors.initials: E
authors.lastname: Gorjup
mesh_terms: D003432:Cross-Linking Reagents / Q000737:chemistry; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D057809:HEK293 Cells; D006801:Humans; D008024:Ligands; D053758:Nanoparticles / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry* / Q000235:genetics; D012709:Serum Albumin / Q000737:chemistry*; D014162:Transfection; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry* / Q000235:genetics
chemical_list: D003432:Cross-Linking Reagents; D008024:Ligands; D009842:Oligopeptides; D012709:Serum Albumin; C568214:arginyl-glycyl-aspartyl-cysteine; D054322:tat Gene Products, Human Immunodeficiency Virus
keywords: albumin; gene delivery; human mesenchymal stem cell; modification; nanoparticle