DNA Nanomachines Explore the Path for Precise Thrombosis Administration

2024-03-18

"Vascular obstructive diseases caused by blood clots have become the deadliest disease in the world. We learned from our communication with clinical doctors that the clinical treatment effect of blood clots is not good at present. Although there are specialized drugs, their side effects are significant and can easily cause vascular bleeding. Therefore, we have been thinking about whether it is possible to accurately deliver drugs to the vicinity of blood clots and administer them in a targeted manner." Professor Wang Lianhui from Nanjing University of Posts and Telecommunications recently introduced an intelligent DNA thrombolysis nanomachine to reporters. This invisible nanomachine can recognize thrombin, a biomarker of blood clots, in blood vessels. By measuring the concentration of thrombin, it can identify whether thrombin comes from a blood clot or a common wound blood clot, and then administer medication to the clot. The related achievements have recently been published in the international academic journal Nature Materials. Wang Lianhui introduced that thrombolytic therapy is currently the preferred treatment option for acute thrombosis such as stroke, myocardial infarction, and pulmonary embolism in clinical practice. Thrombolytic drugs represented by tissue plasminogen activator can activate plasmin in the body, thereby dissolving the main component of thrombus, fibrin. But thrombolytic drugs are a double-edged sword. Overactivated fibrinolytic enzymes can indiscriminately dissolve fibrin, leading to abnormal coagulation function in the body and causing vascular bleeding, such as cerebral hemorrhage. Therefore, precise administration for thrombosis is the future development direction of thrombolytic therapy. Can DNA nanomaterials be used as carriers to accurately deliver drugs to the vicinity of blood clots? Seven years ago, Wang Lianhui's team began developing DNA thrombolysis nanomachines. In this study, researchers created a rectangular DNA nanosheet that was 90 nanometers long and 60 nanometers wide, and then extended a tentacle onto the nanosheet to fix the thrombolytic drug molecules. "Subsequently, the nanosheets were rolled into tubes and DNA nanolocks were made using thrombin aptamers to lock the drug inside the tube, ensuring that the drug would not lose its activity during blood circulation. To open the nanolock, it is necessary to accurately identify blood clots." Wang Lianhui used an analogy, stating that the "key" to unlock the nanolock is a specific molecule that can recognize blood clots - thrombin. "The concentration of thrombin in a blood clot is more than ten times that of a normal wound blood clot. When the thrombin adapter in the nanotube recognizes and calculates the concentration of thrombin to reach the concentration of the blood clot, it will bind with thrombin, thereby opening the 'nanolock' and releasing the drug to the thrombus." Wang Lianhui explained that this method can be accurately administered without causing unnecessary bleeding in the blood vessels. Wang Lianhui introduced that the research team has conducted thrombolysis experiments on cerebral thrombosis, pulmonary thrombosis, arterial thrombosis, and venous thrombosis in mice and rabbits. Compared to clinical thrombolytic drugs, the intelligent DNA thrombolytic nanomachine has increased thrombolytic efficiency in stroke and pulmonary embolism by 3.7 times and 2.1 times, respectively; The complete thrombolysis dose is significantly reduced compared to the tissue plasminogen activation dose; Significantly reducing coagulation abnormalities caused by clinical thrombolytic drugs, extending the treatment window for stroke from 3 hours after symptom onset to 6 hours, this approach is expected to increase the number of stroke patients who receive thrombolytic treatment and benefit from it. "Due to the fact that DNA thrombolysis nanomachines are composed of human bases, they can be degraded by enzymes in the human body and excreted from the body through liver and kidney metabolism."

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