Submission Date

5-5-2026

Document Type

Paper- Restricted to Campus Access

Department

Biochemistry & Molecular Biology

Adviser

Samantha Wilner

Committee Member

Carlita Favero

Committee Member

Amanda Reig

Department Chair

Eric Williamsen

Department Chair

Anthony Lobo

Project Description

Although pharmaceutical labs are developing new drugs quicker than ever, upwards of 90% of these drugs are stalled in the preclinical trial stage because their hydrophobic properties make it difficult for them to reach their target for action. Lipid micelles are nanocarriers with great potential to serve as delivery vehicles for these insoluble drugs, but they are not reliable enough to act on their own since they destabilize in the bloodstream. We propose to use DNA and its binding properties to establish a system through which micelles can be assembled, stabilized, and broken down when appropriate for targeted drug delivery. In this approach, we conjugate short DNA sequences to free lipids and expose them to an aqueous environment in which micelles will assemble. We anticipate that DNA structures will form on the micelle exterior to impart additional stability. Throughout this project, we successfully used phosphoramidite chemistry to activate our lipid starting materials and conjugated these lipids to unique DNA sequences predicted to make defined structures, namely double helices and G-quadruplexes. Next, we purified the conjugates via reverse phase high performance liquid chromatography (RP-HPLC), assembled micelles, and characterized their stability using fluorescence resonance energy transfer (FRET) assays. We also performed gel electrophoresis to better understand the DNA interactions occurring. Our results suggest that G-quadruplex structures impart stability on lipid micelles but that stability is dependent on cargo concentration. Therefore, these G-quadruplex micelles have the potential to be used as a therapeutic method for delivery of hydrophobic drug cargo, but their capacity is likely limited to small molecules with careful dosing to avoid overfilling.

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