Abstract: Objective Modifying 3D tubular DNA origami nanostructures (DONs) onto the mesenchymal stem cells (MSCs) membrane surface to obtain DONs@MSCs. Utilizing the characteristics of MSCs homing lung tissue to achieve targeted delivery of DONs to the lungs of mice. Methods The computer-aided tools for DNA sequence were used to design and obtain obtain pre-designed DONs. The morphology of assembled DONs was characterized by atomic force microscopy(AFM), and the upload of functional groups was verified by agarose gel electrophoresis (AGE). Fluorescent labeled single-strand DNA(ssDNA) was modified on the surface of MSCs using biological orthometabolic sugar engineering. According to the principle of complementary base pairing, DONs were modified on the MSCs surface. Using confocal microscopy and flow cytometry to detect the ssDNA and DONs, and using in vivo imaging to observe the distribution of DONs in lung tissue. Results DONs had been successfully assembled. MSCs membrane surface was successfully modified with ssDNA, and DONs were successfully hybridized to obtain DONs@MSCs. Compared to DONs, the enrichment of DONs@MSCs in the lungs of mice was significantly enhanced. Conclusions DONs@MSCs can be used for DONs targeted delivery to lung tissue of mice. This method provides a new strategy for drug delivery of DONs in lung tissues.

Key words: mesenchymal stem cells, DNA origami nanostructures, targeted delivery