Aptamer Micelles Targeting a Novel Chemokine for Cancer Therapeutics

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 used systematic evolution of ligands by exponential enrichment (SELEX) to develop a single stranded DNA aptamer, FKN-S2, which binds to a novel extracellular chemokine, fractalkine. 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 have synthesized FKN-S2 as an amphiphile by conjugating it to a C16 dialkyl tail and showed that the FKN-S2 aptamer-amphiphiles self-assemble into micelles. This work investigates for the first time the extent and efficacy of using the FKN-S2 aptamer micelles as a targeted delivery vehicle for in vitro and in vivo delivery to fractalkine-expressing mouse colon adenocarcinoma cells. Our in vitro cell binding and trafficking results show that FKN-S2 micelles (functionalized with polyethylene glycol (PEG) or non-PEGylated) can bind and internalize to fractalkine-expressing cancer cells with minimal surface delivery to healthy cells. In addition, our in vivo microPET/CT imaging and biodistribution studies and ex-vivo biodistribution and confocal imaging studies demonstrate that even though both PEGylated FKN-S2 and control micelles can accumulate to the tumor site only the PEGylated FKN-S2 micelles internalize to fractalkine-expressing tumor cancer cells, thus demonstrating the potential of our approach and showing that fractalkine may serve as a specific target for nanoparticle delivery to cancer cells.