Ultrasound-Propelled Janus Rod-Shaped Micromotors for Site-Specific Sonodynamic Thrombolysis

Abstract

Antithrombosis therapy is confronted with short half-lives of thrombolytic agents, limited therapeutic effects, and bleeding complications. Drug delivery systems of thrombolytic agents face challenges in effective penetration into thrombi, which are characterized by well-organized fibrin filled with abundant activated platelets. Herein, Janus rod (JR)-shaped micromotors are constructed by side-by-side electrospinning and cryosection, possessing advantages in controlling the Janus structure and aspect ratio of microrods. Silicon phthalocyanine (Pc) and CaO2 nanoparticles (NPs) are loaded into the separate sides of JRs, and Arg-Gly-Asp (RGD) peptides are grafted on the surface to obtain Pc/Ca@r-JRs for the sonodynamic therapy (SDT) of thrombosis without using any thrombolytic agents. Decomposition of CaO2 NPs ejects O2 bubbles from one side of JRs, and ultrasonication of O2 bubbles produces the cavitation effect, both generating mechanical force to drive the thrombus penetration. The integration of ultrasonication-propelled motion and RGD mediation effectively increases the targeting capabilities of r-JRs to activated platelets. In addition to mechanical thrombolysis, ultrasonication of the released Pc produces 1O2 to destruct fibrin networks of clots. In vitro thrombolysis of whole blood clots shows that ultrasonication of Pc/Ca@r-JRs has a significantly higher thrombolysis rate (73.6%) than those without propelled motion or RGD-mediated clot targeting. In a lower limb thrombosis model, intravenous administration of Pc/Ca@r-JRs indicates 3.4-fold higher accumulations at the clot site than those of JRs, and ultrasonication-propelled motion further increases thrombus retention 2.1 times. Treatment with Pc/Ca@r-JRs and ultrasonication fully removes thrombi and significantly prolongs tail bleeding time. Thus, this study has achieved precise and prompt thrombolysis through selective targeting to clots, efficient penetration into dense networks of thrombi, and SDT-executed thrombolysis.

Applications of Nano/Micromotors for Treatment and Diagnosis in Biological Lumens

“…It could pass through a complex simulated vascular channel. Moreover, Cao et al [ 82 ] constructed Janus rod (JR)-shaped nano/micromotors propelled by the ejection of O2 bubbles and the cavitation effect produced by the ultrasonication of O 2 ( Figure 3 d, Table 3 ). The nano/micromotor could achieve sonodynamic therapy (SDT) of thrombolysis without any other thrombolytic drugs.…”

A Synergistic and Efficient Thrombolytic Nanoplatform: A Mechanical Method of Blasting Combined with Thrombolytic Drugs

“…In addition, excess CREKA polypeptide was incubated with blood clots in the targeted group for 60 min in advance as a blocking group. The blood clots were removed at different time points (15,30,45 and 60 min) and cleaned with PBS. Fluorescence images were immediately collected by a Xenogen IVIS Spectrum imaging system, and their fluorescence intensity was analyzed.…”

The Updated Role of Transcranial Ultrasound Neuromodulation in Ischemic Stroke: From Clinical and Basic Research

“…Indirect thrombolytic effects of TUS mainly enhance the effectiveness of thrombolytic drugs. In addition, ultrasound can directly dissolve the thrombus through its special physical and chemical properties (Cao et al, 2021;Doelare et al, 2021;Mei and Zhang, 2021). The main thrombolytic effects of TUS are summarized as follows.…”