A thorough understanding of nano-bio interactions is critical to design highly effective and targeted drug delivery systems. We have previously designed and prepared methoxy-terminated PEGylated dendron-based copolymers; however, functional handles available for conjugation to bioactive molecules at their surface were lacking. Here we report the synthesis, characterization, and cellular interactions of a set of novel dendron-based copolymers with different end-group functionalities (-NH2, -COOH, and -Ac). 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 it is well known that amine-terminated dendrimers strongly interact nonspecifically with cells, all of the surface-modified dendron micelles exhibited low levels of cellular interactions. 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 nonspecific cellular interactions, the dendron micelles offer a promising drug delivery platform.

Positively charged dendron micelles display negligible cellular interactions

246th National Meeting (2013)

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