Artificial Biomarker-based Feedback-regulated Personalized Precise Thrombolysis with Lower Hemorrhagic Risk

Intravenous thrombolysis possesses critical defects in efficiency and post-thrombolysis hemorrhage due to the current empirical body weight-based medication strategy. However, the inherent heterogeneity of thrombi, instead of body weight, endows thrombi different thrombolysis resistance and affect the thrombolytic outcome. The lack of methods for perceiving thrombolysis resistance has severely hindered the precise medication of vascular embolization. Here, we described the relationship between the thrombin heterogeneity in thrombi and the thrombolysis resistance of thrombi, and created an artificial biomarker-based nano-patrol system to perceive and report the thrombolysis resistance of thrombi taking advantage of the specific recognition and allosteric ability of aptamer-based DNA structure. The nano-patrols are able to accomplish thrombolysis resistance-matched personalized precise therapy through the NIR-Ⅱ laser-regulated synergistic thrombolytic effect, according to the feedback signal from artificial biomarkers. This new strategy depicted enhanced thrombolytic efficiency than alteplase for rats, mini pigs and clinical thrombi, achieved recanalization in thrombotic model where alteplase encountered failure. Moreover, the nano-patrol system remarkably reduced the infarct volume and the hemorrhagic transformation risk (0.12-fold of alteplase) of cerebral thrombosis. This nano-patrol system developed new tool for the assessment of thrombolysis resistance and personalized precise thrombolysis with lower hemorrhagic risk. Inject the corresponding drug (saline, rt-PA, Nano-patrol+NIR) 4.5 hours after modeling, and take brain tissue for testing three days later