A surface-modified dendrimer set for potential application as drug delivery vehicles: synthesis, in vitro toxicity, and intracellular localization.
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.
Freie Universität Berlin, Institut für Chemie/Organische Chemie, Takustrasse 3, 14195 Berlin, Germany.
Sabine
S
Fuchs
Timo
T
Kapp
Henning
H
Otto
Torsten
T
Schöneberg
Peter
P
Franke
Ronald
R
Gust
A Dieter
AD
Schlüter
D000596:Amino Acids / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D046911:Macromolecular Substances; D018613:Microscopy, Confocal / Q000379:methods; D015394:Molecular Structure; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D013499:Surface Properties
D000596:Amino Acids; D004337:Drug Carriers; D008024:Ligands; D046911:Macromolecular Substances; D011073:Polyamines