Targeted and reversible cancer cell-binding DNA nanoparticles

DNA nanoparticles (DeNAno) produced by rolling circle replication of circular oligonucleotide templates are a novel format for the selection of cell-binding reagents from randomized libraries. DeNAno particles consist of several hundred concatemers and can leverage that multivalency to bind to complex surfaces such as cells. In this study, an iterative bio-panning approach was used to recover particles that bound to the mouse pancreatic cancer line, Panc-02. These particles shared a primary sequence motif. Hybridization of a locked nucleic acid complimentary to this motif both inhibited cell binding and released pre-bound DeNAno particles from the cells. The monomeric form of one of the selected sequences was unable to compete with the cognate particle, consistent with a low-affinity, but high-avidity, type interaction. DeNAno library selection against cancer or other cell types can, thus, yield novel cell binding agents without a priori knowledge of particular cell surface molecules.