Authors: I. Lee, B.D. Athey, A.W. Wetzel and J.R. Baker Jr.
Affilation: University of Michigan, United States
Pages: 13 - 16
Keywords: molecular dynamics simulation, dendrimer, folic acid, fluorescein
Molecular dynamics simulations on PAMAM dendrimers were performed to design and optimize the condition for cancer cell targeting and imaging. Folic acid and fluorescein-conjugated dendrimers with a primary amine surface group (without capping) and with a carboxyl group showed local branch aggregation, implying less solubility in water. Simulations indicated that folic acid conjugates on the acetamide surface tend to extend out, while most folic acids on the hydroxyl surface are buried in the dendrimer, predicting less potential interaction with folate receptors on the surface of cells. These results strongly suggest that the acetamide capping group for folic acid and fluorescein-conjugated dendrimers optimal for targeting, a finding supported by cellular targeting experiments using flow cytometry and 3-D confocal microscopy. Our computer simulation results have informed nanomolecular synthesis, and have led to structures which exhibit desired biologic activity.