Microstructure of dendrimers functionalized with folic acid as studied by molecular dynamics simulations

Abstract

Poly(amidoamine) dendrimers (PAMAM), due to their unique properties such as nanometric size and shape, monodispersity, and numerous modifiable surface groups, are promising nanocarriers in a wide range of biomedical applications. However, amine-terminated PAMAM dendrimers have been proven to be toxic at physiological pH, which limits their biomedical application. It has been approved that the binding of folic acid (FA) to dendrimer reduces nanocarrier toxicity. Also, it can selectively target cancer cells with folate receptors (FR-α) overexpression. In this study, we have explored the structural features of FA-functionalized PAMAM dendrimers using all-atom molecular dynamics (MD) simulations. To this end, third and fourth generations of PAMAM dendrimers were functionalized with FA, and MD simulations were performed for 100 ns at 310 K and 1 bar at neutral pH. We have examined the effect of FA functionalization on the molecular size, solvent accessible surface area, structural changes of amidoamine monomers, and the solvation of investigated dendrimers. Our results reveal that G4FA is the most suitable drug delivery system for cancer therapy among others.