Abstract
PEGylated dendron-based copolymers (PDC) with different end-group functionalities (-NH(2), -COOH, and -Ac) were synthesized and self-assembled into dendron micelles to investigate the effect of terminal surface charges on size, morphology, and cellular interactions of the micelles. All of the dendron micelles exhibited similar sizes (20-60 nm) and spherical morphologies, as measured using dynamic light scattering and transmission electron microscopy, respectively. The cellular interactions of dendron micelles were evaluated using confocal microscopy and flow cytometry. Surprisingly, although amine-terminated dendrimers are known to strongly interact with cells non-specifically, all of the surface-modified dendron micelles exhibited charge-independent low-levels of cellular interaction. The unexpected results, particularly from the amine-terminated dendron micelles, could be attributed to: i) minimal end-group effects, as each PDC has an approximately 10-fold lower charge-number-to-molecular-weight ratio compared to the dendrimer; and ii) intra- and intermolecular hydrogen bonding between positively charged terminal groups with poly(ethylene glycol) (PEG) backbones, which leads to the sequestration of the charges, as demonstrated by atomistic molecular dynamics simulations. With the narrow size distribution, uniform morphologies, and low levels of non-specific cellular interactions, the dendron micelles offer a promising drug delivery platform.