Self-Assembled DNA Nanocentipede as Multivalent Drug Carrier for Targeted Delivery

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Abstract

An idea drug carrier, with good binding affinity, selectivity, drug payload capacity, and cellular internalized capability, will greatly improve the efficiency of target delivery. Herein a self-assembled and multivalent DNA nanostructure was developed as drug carrier for efficient and targeted delivery. The DNA structure was similar to that of a centipede, composed of trunk and legs: The trunk was a self-assembled DNA scaffold via hybridization chain reaction (HCR) from two biotinylated hairpin monomers created upon initiation by a trigger DNA, and the legs were biotinylated aptamers conjugated to the trunk via streptavidin-biotin affinity interaction. The long trunk of the "DNA nanocentipede" was loaded with doxorubicin (Dox), and the legs were SMMC-7721 cell-binding aptamers (Zy1) which functioned as targeting moieties to firmly and selectively grasp target cells. The results of agarose gel electrophoresis and fluorescence anisotropy confirmed that Zy1-based DNA nanocentipedes (Zy1-Nces) were successfully constructed. Flow cytometric analyses demonstrated that Zy1-Nces were more effective than free Zy1 in binding affinity and selectivity due to a multivalent effect. Confocal microscopy studies demonstrated that the internalization was highly dependent on the higher valences of DNA nanocentipedes without the loss of selectivity. Meanwhile, Zy1-Nces exhibited high drug-loading capacity and selective drug transport. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed enhanced cellular cytotoxicity of the Dox-loaded Zy1-Nces (Zy1-Nces-Dox) to the target SMMC-7721 cells but not negative control L02 cells. This approach is applicable to prepare drug carriers for other targets by construction of the nanocentipedes with relevant nucleic acid fragments.

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