Simple Self-Assembled Targeting DNA Nano Sea Urchin as a Multivalent Drug Carrier.

Abstract

An ideal drug delivery platform with high cell selectivity, drug payload capacity, and cellular internalization capability is usually of the essence for targeted cancer chemotherapy. Herein, by combining palindromic DNA strands with a targeting aptamer probe, we demonstrated a self-assembled nanoscale sea urchin-shaped structure (called aptamer-NSU) as a multivalent carrier capable of executing targeted cancer cell imaging and drug delivery. The DNA nanostructure is composed of a spherical trunk and surface-confined spines: the former is assembled from only one biotinylated DNA containing four different palindrome domains, and the latter is a biotinylated aptamer (Sgc8) conjugated to the trunk surface via streptavidin-biotin affinity interaction. The spherical trunk can densely load doxorubicin (Dox), and the surface-confined Sgc8 probes can function as targeting moieties to specifically bind to target cells in a polyvalent-binding fashion. Atomic force microscopy (AFM) and gel electrophoresis show the assembly of Sgc8-NSU. The confocal fluorescence imaging demonstrates that fluorescently labeled Sgc8-NSU can specifically image CEM cells. Flow cytometric analyses indicate that Sgc8-NSU exhibits the multivalent binding effect, achieving the significant improvement in binding affinity and selectivity compared with free Sgc8. Moreover, the CCK-8 assay confirmed that Dox-loaded Sgc8-NSU induces an enhanced cellular cytotoxicity to target cancer cells but not to negative nontarget cells. The developed DNA nanoplatform is expected to provide a valuable insight into constructing structural DNA nanotechnology-based drug delivery nanovehicles suitable for targeted cancer therapy.