Study on the biosafety and in vivo metabolic patterns of DNA-inspired Janus Base nanotubes

Janus base nanotubes (JBNTs), also known as Rosette nanotubes, are synthesized from DNA-inspired base molecular monomers and show promise for biomedical applications. However, their clinical translation has been hindered by a lack of comprehensive biocompatibility and biodistribution studies. In this study, we evaluated the in vitro and in vivo biocompatibility of JBNTs and their biodistribution following intravenous and knee intra-articular injections. Within the concentration range of 40 microg/mL, JBNTs supported excellent cell growth with no significant inflammatory response, and even at a concentration of 100 microg/mL, no noticeable erythrocyte hemolysis was observed. In vivo biocompatibility assessment revealed that intravenous injection of 30 microg and 150 microg of JBNTs did not result in significant abnormalities in routine blood tests, inflammatory responses, or organ damage within 7 days. JBNTs were primarily metabolized by the liver and kidneys, with excretion occurring via urine and feces. Notably, we observed that JBNTs extended the retention time of macromolecular substances within the knee joint cavity. While Cy7 alone remained in the joint for approximately 3 days, JBNTs-Cy7 persisted for more than 21 days. This study underscores the safety, efficacy, and transformative potential of JBNTs for clinical applications in targeted drug delivery and tissue regeneration.