BHU, Varanasi
Debabrata Dash is at Banaras Hindu University since 1986. For last three decades, he has been engaged in the study of platelet signalling, thrombus biology and biomedical applications of nanomaterials, results of which have been published in ACS Nano, Biosensors Bioelectronics, Nanomedicine, JBC, FASEB Journal and Molecular Medicine. He is a recipient of the Sun Pharma Research Award, Prof. C N R Rao Award for Excellence in Scientific Research, ICMR-Basanti Devi Amir Chand Award, and many others. He is Fellow of IASc (2015), INSA and National Academy of Medical Sciences.
Session 1C: Inaugural Lectures by Fellows/Associates
Chairperson: Saumitra Das, Indian Institute of Science, Bengaluru
Killing thrombus with nano-bullets View Presentation / View Video
Fibrinolytic therapy for arterial or venous thrombotic disorders warrants systemic administration of thrombolytics like streptokinase, which is associated with serious bleeding complications. In their study, the speaker’s group provided proof-of-concept of photothermal ablation of thrombus. Thrombi were generated in vitro from purified fibrinogen, or in vivo in murine blood vessels. Gold nanorods were added on fibrin-rich clots in vitro, followed by irradiation with a 808 nm near-infrared laser source at power density 1.05W/cm2. Local rise in temperature (up to 55–65oC) was monitored with an infrared thermal camera that led to nearly 30% lysis of clot. The extent of lysis under arterial shear was higher than that at venous shear. Superficial femoral veins were exposed in mice and thrombus formation was induced by topical application of FeCl3. Anti-fibrin antibody-conjugated gold nanorods, which target fibrin-rich thrombi, were injected in mice. NIR-laser irradiation of exposed femoral veins containing thrombi led to clot degradation and the re-establishment of vascular patency, which was demonstrated by the restored blood flow recorded in Doppler spectral scans, as well as histopathological investigations. This is the first report on application of photothermal therapy as an anti-thrombotic measure. Remarkably, addition of streptokinase has a multimodal additive effect in accelerating the photothermal lysis of thrombi (up to 40%) even at a dose significantly lower (by 30 to 50 times) than therapeutic concentration, thus minimizing life-threatening side effects and adverse complications. This combinatorial approach has great potential in bringing about lysis of pathological clots that can effectively overcome the drawbacks of existing therapies.