Efficacy of a SIRT1 Aptamer as an Anti-Angiogenic and Antioxidant Agent in in vitro, ex vivo, and in vivo Models

Background: Angiogenesis and oxidative stress are closely related processes that facilitate pathological vascular remodeling and cancer progression. Given that sirtuin 1 (SIRT1) modulates endothelial function, redox balance, and angiogenic remodeling in a context-dependent manner. Objective: To investigate the anti-angiogenic and antioxidant activity of a circular SIRT1 aptamer in multidesign settings. Methods: The endothelial response was evaluated in HUVECs via the XTT assay; antioxidant activity was assessed using the DPPH radical scavenging assay; ex vivo angiogenesis was measured in the rat aortic ring model; and in vivo validation was conducted with the chick chorioallantoic membrane (CAM) assay. Results: The impact of the aptamer on HUVEC was concentration- and time-dependent, with IC50 values of 3.910, 3.103, and 1.337 µM at 24, 48, and 72 hours, respectively. Furthermore, the aptamer exhibited substantial radical-scavenging activity in the DPPH assay, representing an IC50 of 0.0499 µM. It also inhibited microvessel sprouting in the rat aortic ring assay, with an IC50 of 0.613 µM, and suppressed CAM vascularization in a dose-dependent manner; the highest concentration tested produced an effect comparable to that of aspirin. These findings indicate that the circular SIRT1 aptamer possesses anti-angiogenic properties across in vitro, ex vivo, and in vivo models, in addition to its antioxidant capacity within cell-free systems. Conclusions: This aptamer has potential to act as a bioactive oligonucleotide scaffold for angiogenic applications; however, further research is necessary to determine its target specificity and translational significance.