DNA tetrahedron nanoparticles enable kidney function assessment in mice with unilateral ureteral obstruction

Objectives: As one of the elegant examples of DNA nanostructures, DNA tetrahedron nanoparticle (DTN) has been used for biosensing, imaging, and treatment of cancer. To facilitate potential biomedical application of DTN, fundamental understanding of the biological properties of DTN in animals becomes increasingly important. In this study, we aim to investigate the biodistribution and pharmacokinetics of DTN in animals and apply DTN for kidney function evaluation in healthy mice and mice with unilateral ureteral obstruction (UUO).

Methods: DTN with 4 side-arms was assembled through a one-step annealing process and characterized using gel electrophoresis. After hybridization with Dylight755-ssDNA or ⁶⁴Cu-NOTA-ssDNA, Dylight755-DTN or ⁶⁴Cu-DTN was then applied for fluorescent imaging and dynamic PET imaging of healthy mice. A murine model of UUO was prepared by surgically ligating the left ureter. Dynamic PET imaging of UUO mice using ⁶⁴Cu-DTN was performed to not only validate but also quantify the renal clearance and biodistribution of DTN in vivo.

Results: Dylight755-DTN and ⁶⁴Cu-DTN could be well prepared and characterized. Fluorescent imaging revealed the efficient renal clearance of DTN in healthy mice, and dynamic PET imaging confirmed that a majority of DTN undertook urine excretion and accumulated in the bladder. Dynamic PET imaging of UUO mice presented distinct uptake patterns and transportation kinetics of DTN in the obstructed and contralateral kidneys. After analyzing the time-activity curve of kidneys based on PET imaging, we were able to systematically compare the renal perfusion and excretion speed of kidneys in healthy mice and mice with UUO in a non-invasive manner. Conclusion: With Dylight755-DTN for fluorescent imaging and ⁶⁴Cu-DTN for PET imaging, real-time and quantitative biological understanding of DTN in animals was established. Efficient renal clearance of DTN further enabled kidney function evaluation of mice with unilateral ureteral obstruction, allowing for the correlate renal dysfunction with the changes of the renal time-activity curve in vivo.

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