(448f) Development of Aptamer-Amphiphiles for Targeted Delivery to Colon Cancer Cells Expressing Fractalkine
AIChE Annual Meeting
Wednesday, October 19, 2011 - 10:20am to 10:40am
Delivering chemotherapeutic drugs directly to cancerous tissues would greatly improve patient outcomes and reduce debilitating side effects. To accomplish this, we developed an aptamer which binds to fractalkine with high affinity through the Systematic Evolution of Ligands by Exponential Enrichment, or SELEX process. Fractalkine is an exciting cell surface protein uniquely suited for targeted delivery. Fractalkine, expressed on tumor vasculature and certain cancers like colon cancer, is designed to capture leukocytes from circulation. The binding domain sits atop a mucin-like stalk extending the domain away from the cell surface allowing for maximum interaction with the circulating leukocytes or a targeted delivery vehicle. Aptamers are short single stranded nucleic acid sequences which bind to a target protein through hydrogen bonding, ring stacking, electrostatic and van der Waals forces. Aptamers have only recently been used as targeting moieties yet have many benefits over other ligands. Aptamers have binding affinities and specificities rivaling that of antibodies yet are a tenth the size, are easily obtained through automated DNA synthesis and have little to no immunogenicity.
The developed aptamer has high affinity for fractalkine as demonstrated through ELISA and cell based fluorescent assays. For use with liposome delivery vehicle, the aptamer was conjugated to a hydrophobic tail creating an aptamer-amphiphile which readily incorporates into the liposome lipid bilayer. The mild chemistry allows for conjugation of a wide range of hydrophobic molecules with little risk of degradation of the aptamer. Confocal microscopy and flow cytometry quantify the targeting capabilities of the aptamer functionalized liposomes to colon cancer cells expressing high levels of fractalkine while leaving healthy cells unaffected. This work demonstrates exciting possibilities for aptamer targeted delivery to fractalkine.