title: Differential uptake of nanoparticles by endothelial cells through polyelectrolytes with affinity for caveolae.
abstract: Nanoparticles (NPs) constitute an important medium for the targeted delivery of cancer therapeutics. Targeting of NPs to a specific cell type is traditionally achieved through the modification of the NP surface with peptides, aptamers, or other motifs that specifically recognize a cell-surface receptor, leading to internalization of NPs via clathrin and caveolae-mediated endocytosis. We have discovered that modifying the NP surface with anionic polyelectrolytes of varying lipophilicity can regulate the uptake of lipid NPs by endothelial and epithelial cells. Furthermore, we report the finding that synthetic polyelectrolytes composed of an aromatic sulfonic acid backbone exhibit specific affinity for caveolae of endothelial cells. By exploiting the higher expression of caveolae in endothelial cells in comparison with epithelial cells, a purely physiochemical approach to the targeted uptake of lipid NPs to endothelial cells is demonstrated. The ability to confer preferential affinity for NPs to cell surface domains by varying the charge and lipophilic characteristics of an NP surface offers a general means of achieving targeted delivery without the need for receptor-ligand-type targeting strategies.
authors: Institute for Macromolecular Chemistry, Hermann Staudinger Haus, University of Freiburg, 79104 Freiburg, Germany.
authors: Julia
authors: J
authors: Voigt
authors: Jon
authors: J
authors: Christensen
authors: V Prasad
authors: VP
authors: Shastri
mesh_terms: D000818:Animals; D015153:Blotting, Western; D021941:Caveolae / Q000378:metabolism*; D002460:Cell Line; D002616:Chemical Engineering / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods*; D004573:Electrolytes / Q000378:metabolism* / Q000493:pharmacokinetics; D042783:Endothelial Cells / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000378:metabolism* / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy*; D011108:Polymers / Q000378:metabolism* / Q000493:pharmacokinetics; D060888:Real-Time Polymerase Chain Reaction; D055672:Static Electricity; D013451:Sulfonic Acids / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D004573:Electrolytes; D011108:Polymers; D013451:Sulfonic Acids; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue
keywords: aromatic polysulfonates; polyanion; polystyrene sulfonate; vasculature