Abstract 1667 Aptamer-Targeted Dendrimersomes Assembled from Azido-Modified Janus Dendrimers "Clicked" to DNA

Amphiphilic Janus dendrimers (JDs) are constructed from hydrophobic and hydrophilic dendrons, providing a synthetic alternative to lipids in drug delivery applications. These JDs self-assemble into vesicles called dendrimersomes (DSs) with tunable structural characteristics and can encapsulate both hydrophobic cargo as well as nucleic acids. Compared to liposomes, DSs demonstrate enhanced stability due to increased intermolecular interactions between aromatic branching centers and due to an increase in the number of hydrophobic chains per molecule. Despite these attractive characteristics, drug delivery functionality is limited because decorating the periphery of DSs with biomacromolecules such as proteins and nucleic acids remains a challenge. Here, we report the successful conjugation of azide-modified JDs to alkyne-modified DNAs using copper-catalyzed click chemistry. These 16-nucleotide DNA sequences serve as anchors for the subsequent hybridization of DNA aptamers. We demonstrate that DNA-functionalized JDs form nanometer sized DSs in aqueous solution via thin film hydration. These vesicles, now displaying short DNAs, are then hybridized to anti-transferrin receptor DNA aptamers. Aptamer-targeted DSs show enhanced cellular uptake as compared to control vesicles via fluorescence microscopy and flow cytometry. This work demonstrates the versatility of using click chemistry to conjugate functionalized JDs with biologically relevant molecules and the feasibility of targeting DNA-modified DSs for drug delivery applications.