A Surface-Modified Dendrimer Set for Potential Application as Drug Delivery Vehicles: Synthesis, In Vitro Toxicity, and Intracellular Localization

• Published in: Chemistry : a European journal 2004-03, Vol.10 (5), p.1167-1192
• Main Authors: Fuchs, Sabine, Kapp, Timo, Otto, Henning, Schöneberg, Torsten, Franke, Peter, Gust, Ronald, Schlüter, A. Dieter
• Format: Article
• Language: English
• Subjects: Amino Acids - chemistry; Cell Line, Tumor; Cell Survival - drug effects; Cell Survival - physiology; cellular uptake; cytotoxicity; dendrimers; Drug Carriers - chemical synthesis; Drug Carriers - chemistry; Drug Carriers - toxicity; drug delivery; HeLa Cells; Humans; Ligands; Macromolecular Substances; Microscopy, Confocal - methods; Molecular Structure; Polyamines - chemical synthesis; Polyamines - chemistry; Polyamines - toxicity; Surface Properties; synthesis
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.200305386

The synthesis, cytotoxicity, and behavior in cell culture of a new set of first‐ (G1) and second‐generation (G2) dendrimers is reported. The surface functionality of these dendrimers has been varied to see whether structure/toxicity relations can be observed. The outermost functional groups are amines that are decorated either with protons, tert‐butoxycarbonyl (Boc) or benzyloxycarbonyl (Cbz) protecting groups, Boc‐protected or unprotected natural amino acid residues, ethylenediamine ligands, and/or dansyl fluorescence labels. The cytotoxicity was determined in vitro in concentration‐dependent assays using the human MCF‐7 breast cancer cell line. Cellular uptake and intracellular distribution was monitored by confocal fluorescence microscopy after internalization of the dansyl‐labeled dendrimers by HeLa cells. Highly water‐soluble dendrimers carrying either free propylamines, natural amino acids, such as L‐methionine, L‐phenylalanine, and L‐aspartic acid, or ethylenediamine ligands were synthesized and then examined in cell culture. Attachment of a fluorescence marker (dansyl) to the surface of the dendrimers allowed their cellular uptake to be monitored with confocal fluorescence microscopy (see picture). The in vitro cytotoxicity of all synthesized dendrimers was investigated to see whether they can be used as potential drug carriers.