title: Tuftsin-modified alginate nanoparticles as a noncondensing macrophage-targeted DNA delivery system.
abstract: The main objective of this study was to evaluate macrophage-targeted alginate nanoparticles as a noncondensing gene delivery system for potential anti-inflammatory therapy. An external gelation method was employed to form plasmid DNA-encapsulated alginate nanoparticles. The nanoparticle surface was modified with a peptide sequence containing tuftsin (TKPR), and transfection efficiency was determined in J774A.1 macrophages. The effect of transfected mIL-10 in blocking expression of tumor necrosis factor-alpha (TNF-α) was evaluated in lipopolysaccharide (LPS)-stimulated cells. Scrambled peptide- and tuftsin-modified cross-linked alginate nanoparticles efficiently encapsulated plasmid DNA and protected against DNase I degradation. The transgene expression efficiencies, measured using GFP and mIL-10 expressing plasmid DNA, were highest with tuftsin-modified nanoparticles. Levels of TNF-α were significantly lower (p < 0.0001) in LPS-stimulated cells that were transfected with mIL-10 using alginate nanoparticles. The results of the study show that noncondensing alginate nanoparticles can efficiently deliver plasmid DNA, leading to sustained in vitro gene expression in macrophages.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, Massachusetts 02115, United States.
authors.forename: Shardool
authors.initials: S
authors.lastname: Jain
authors.forename: Mansoor
authors.initials: M
authors.lastname: Amiji
mesh_terms: D000464:Alginates / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D003432:Cross-Linking Reagents / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003850:Deoxyribonuclease I / Q000378:metabolism; D018014:Gene Transfer Techniques; D020723:Glucuronic Acid / Q000737:chemistry / Q000378:metabolism; D006603:Hexuronic Acids / Q000737:chemistry / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010957:Plasmids; D014405:Tuftsin / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000464:Alginates; D003432:Cross-Linking Reagents; D006603:Hexuronic Acids; D020723:Glucuronic Acid; D004247:DNA; D003850:Deoxyribonuclease I; D014405:Tuftsin