Effects of PEGylation on the Size and Internal Structure of Dendrimers: Self-Penetration of Long PEG Chains into the Dendrimer Core

G4 PAMAM dendrimers grafted with poly(ethylene glycol) (PEG) of different sizes (M-w = 550 and 5000) and grafting densities (12-94% of surface terminals) were simulated using the coarse-grained (CG) force fields previously developed and reparametrized in this work. Simulations are carried out for G4, G5, and G7 un-PEGylated dendrimers that are either unprotonated, terminally protonated, or protonated on both terminals and interior sites, corresponding to pH values of > 10, 7, and < 5, respectively. As protonation increases, simulations show only a small (similar to 6% for G4 and G5) change of dendrimer radius of gyration R-g and show a structural transition from dense-core to dense-shell structure, both of which are in agreement with recent scattering experiments and all-atom simulations. For the PEGylated dendrimers, the R-g of the fully PEG(M-w = 5000)-grafted dendrimer also agrees well with experiment. Longer PEG chains with higher grafting density yield PEG PEG crowding, which stretches dendrimer terminals toward water more strongly, leading to larger size and a dense-shell structure of the dendrimer. Long PEG chains at high grafting densities also penetrate into the dendrimer core, while short ones do not, which might help explain the reduced encapsulation of hydrophobic compounds seen experimentally in dendrimers that are 75%-grafted with long PEG's (M-w = 5000). This reduced encapsulation for dendrimers with long grafted PEG's has previously been attributed to PEG-induced dendrimer aggregation, but this explanation is not consistent with our previous simulations which showed no aggregation even with long PEG's but is consistent with the new simulations reported here that show PEG penetration into the core of the dendrimer to which the PEG is attached.