Evaluation of Pharmacokinetics, Immunogenicity, and Immunotoxicity of DNA Tetrahedral and DNA Polymeric Nanostructures

Abstract Deoxyribonucleic acid (DNA) nanostructures have been extensively explored in biomedical applications and have emerged as a promising platform for drug delivery, bioanalysis, and therapeutics. Their in vivo behaviors have received much attention, a prerequisite for clinical applications. Herein, the pharmacokinetics, immunogenicity, and immunotoxicity of two representative DNA nanostructures: DNA tetrahedron (TDN) and DNA nanoparticle (DNP) are studied. The pharmacokinetics of DNA nanostructures are monitored in a mouse model via tracking of 32 P radiolabeled, and the half‐lives of TDN and DNP are 9.88 and 19.80 min, respectively. TDN and DNP preferentially accumulate in the liver and kidney in one half‐life and are metabolized through liver, kidney, and excreta after 24 h. Meanwhile, TDN and DNP elicit a weak pro‐inflammatory immune response with low immunogenicity and are non‐immunotoxic, as shown by immunotoxicity evaluation, histopathology, and serum biochemical index analysis. This research shows that the DNA nanostructures of TDN and DNP are safe for biological systems, indicating that TDN and DNP can be developed as promising therapeutic platforms in biomedicine.