Submission Date

4-24-2023

Document Type

Paper- Restricted to Campus Access

Department

Biochemistry & Molecular Biology

Adviser

Samantha Wilner

Committee Member

Amanda Reig

Committee Member

Rebecca Evans

Department Chair

Eric Williamsen

Department Chair

Anthony Lobo

Project Description

Among the current selection of modern drugs, most are hydrophobic causing insolubility in the bloodstream. In order to improve solubility, vesicles similar to a cell’s lipid bilayer can be formed to carry the hydrophobic cargo to targeted tissues. In these vesicles, hydrophilic head groups face the aqueous surroundings while hydrophobic tails along with any associated hydrophobic drugs remain protected. These vesicles can then deliver cargo to cells via membrane fusion or receptor-mediated endocytosis, thus improving delivery of poorly soluble drugs. Janus dendrimers (JDs) are branched amphipathic polymers that self-assemble into vesicles called dendrimersomes (DSs) and provide an attractive synthetic alternative to lipids in drug delivery applications. Here, we demonstrate that DSs can be delivered to cells in a targeted manner using DNA aptamers. First, we report the successful conjugation of azide-modified JDs to alkyne-modified DNAs using copper-catalyzed click chemistry. We show that these DNA-modified JDs self-assemble into DSs via thin film hydration. These vesicles, now displaying short DNAs around their periphery, 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.

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