Accelerating thrombolysis using a precision and clot-penetrating drug delivery strategy by nanoparticle-shelled microbubbles
July 29, 2020 — Science Advances
Conventional thrombolytic drugs for vascular blockage such as tissue plasminogen activator (tPA) are challenged by the low bioavailability, off-target side effects and limited penetration in thrombi, leading to delayed recanalization. We hypothesize that these challenges can be addressed with the targeted and controlled delivery of thrombolytic drugs or precision drug delivery. A porous and magnetic microbubble platform is developed to formulate tPA. This system can maintain the tPA activity during circulation, be magnetically guided to the thrombi, and then remotely activated for drug release. The ultrasound stimulation also improves the drug penetration into thrombi. In a mouse model of venous thrombosis, the residual thrombus decreased by 67.5% when compared to conventional injection of tPA. The penetration of tPA by ultrasound was up to several hundred micrometers in thrombi. This strategy not only improves the therapeutic efficacy but also accelerates the lytic rate, enabling it to be promising in time-critical thrombolytic therapy.
Authors: Siyu Wang1, Xixi Guo1, Weijun Xiu1, Yang Liu2, Lili Ren1, Huaxin Xiao1
1Key Laboratory for Organic Electronics and Information Displays and Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM), Jiangsu National Synergistic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts and Telecommunications, Nanjing, China.
2State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China.
3School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore
Vol. 6, no. 31, eaaz8204; DOI: 10.1126/sciadv.aaz8204
Read full text at: https://advances.sciencemag.org/content/6/31/eaaz8204