There is a growing need for cancer therapeutics to be delivered without off-target side effects; in order to do this, the cancer cells must express a unique target. We have previously developed a single stranded DNA (ssDNA) aptamer, FKN-S2, that binds to a novel extracellular chemokine, fractalkine, with high affinity and specificity. Unlike other chemokines, fractalkine has been shown to act as an adhesion molecule and is expressed on inflamed and cancerous cells thus making it a promising target for cancer therapeutics. We synthesized the FKN-S2 as an aptamer-amphiphile and showed that self-assembles into 18 nm micelles. The FKN-S2 micelles decorated with polyethylene glycol (PEG) were delivered to mouse colon adenocarcinoma cells that expressed human fractalkine (MCA-38.FKN) as well as control healthy cells in vitro, and only the MCA-38.FKN cells were shown to internalize the micelles.The MCA-38.FKN cells were subcutaneously injected into nude female mice to create xenograft tumors for in vivo experiments. The biodistribution and uptake of FKN-S2 PEGylated micelles was compared to random ssDNA-amphiphile PEGylated micelles using 64Cu-labeling for in vivo micro positron emission tomography (µPET)/computerized tomography (CT) imaging, and fluorescence labeling for ex vivo confocal microscopy imaging. Although the biodistribution of the two micelles was the same, ex vivo confocal microscopy showed that only the FKN-S2 micelles were capable of internalizing into the tumor cells. This is the first demonstration of a ssDNA aptamer, or any other ligand being used to target fractalkine for in vitro and in vivo delivery of nanoparticles to fractalkine-expressing cells, and shows that the FKN-S2 micelles may serve as a valuable tool for developing targeted therapies in the future.

Aptamer micelles targeting cancer cells expressing the chemokine fractalkine

254th National Meeting (2017)

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