Cell surface proteins can play important roles in cancer pathogenesis. Comprehensive understanding of the surface protein expression patterns of tumor cells and, consequently, the pathogenesis of tumor cells, depends on molecular probes against these proteins. To be effectively used for tumor diagnosis, classification and therapy, such probes would be capable of specific binding to targeted tumor cells. Molecular aptamers, designer DNA/RNA probes, can address this challenge by recognizing proteins, peptides and other small molecules with high affinity and specificity. Through a process known as cell-SELEX, we used live acute myeloid leukemia (AML) cells to select a group of DNA aptamers that can recognize acute myeloid leukemia cells with dissociation constants (Kds) in the nanomolar range. Interestingly, one aptamer (KH1C12), compared with two control cell lines (K562 and NB4), showed significant selectivity to the target AML cell line (HL60) and could recognize the target cells within a complex mixture of normal bone marrow aspirates. The other two aptamers KK1B10 and KK1D04 recognize targets associated with monocytic differentiation. Our studies demonstrate that the selected aptamers can be used as a molecular tool for further understanding surface protein expression patterns on tumor cells and thus providing a foundation for effective molecular analysis of leukemia and its subcategories.

One important issue using cells as therapeutics is targeted delivery. Engineering cell surfaces to improve delivery efficiency is thus of great interest. Here we report a simple, efficient and effective way to modify the cell surface with target-specific ligands, i.e., DNA aptamers, while minimizing the effects on the modified cells. We demonstrated that after incubating with lipo-aptamer probes (shown in expansion), immune cells (red) recognize cancer cells (blue) in the cell mixture, and kill cancer cells.

No abstract