Highly hydrophilic PEG-dendron labeled hybrids

Developing polymeric drug delivery systems requires precise design of synthetic polymers, which can be functionalized with drug molecules. Such polymeric systems can potentially target hydrophobic drugs to the site of disease. Dendrimers offer great advantages as delivery systems due to their globular size, monodispersity and highly tunable properties. However, due to the hydrophobicity of many drug molecules, not all the dendritic end-groups can be functionalized with drug moieties. Importantly, it was recently reported that labeling the periphery of PAMAM dendrimer gives mixtures of labeled products with different numbers of fluorescent dyes on the surface.¹ Moreover, each of the formed species showed different cell internalization capability, demonstrating the need for the development of more precise methodologies for the functionalization of dendrimers with hydrophobic drug molecules. To address this challenge and gain control over the size of the dendrimer and the number of conjugated drugs without impairing the monodispersity of the system, we designed highly hydrophilic PEG-dendron hybrids with internal binding sites. We labeled these hydrophilic hybrids with different dyes in order to compare our internal-loading approach to the common loading of the end-groups at the periphery of the dendrimer.

Reference:

1. Dougherty, C. A., Vaidyanathan, S., Orr, B. G. & Banaszak Holl, M. M. Fluorophore:Dendrimer Ratio Impacts Cellular Uptake and Intracellular Fluorescence Lifetime. Bioconjug. Chem. 26, 304–315 (2015).