Abstract
Microbubbles with enhanced ultrasound represent a potentially potent evolution to the administration of a free drug in the treatment of thrombotic diseases. Conformational and expressional changes of several thrombotic biological components during active coagulation provide epitopes that allow site-specific delivery of microbubble-based agents to the thrombus for theranostic purpose. Through the interaction with these epitopes, emerging high-affinity small molecular ligands are able to selectively target the thrombi with tremendous advantages over traditional antibody-based strategy. In this mini-review, we summarize recent novel strategies for microbubble-based targeting of thrombus through epitopes located at activated platelets and fibrin. We also discuss the challenges of current targeting modalities and supramolecular carrier systems for their translational use in thrombotic pathologies.
Highlights
Cardiovascular disease (CVD) remains the top cause of death worldwide and accounts for more than 40% of deaths in China (Liu et al, 2019)
Wang et al (2020) reported the decrease of residual thrombus by 67.5% and higher drug penetration in microbubble-based tissue plasminogen activator (tPA) delivery system when compared to conventional systemic administration of tPA, highlighting the advantageous therapeutic efficacy in time-critical thrombolytic therapy
We present a brief overview of the strategies available to implement the thrombus-specific targeting function of microbubbles
Summary
Cardiovascular disease (CVD) remains the top cause of death worldwide and accounts for more than 40% of deaths in China (Liu et al, 2019). The recognized significance of thrombosis in the pathogenesis of CVD has led to a great clinical demand for thrombusspecific agents that aid in the targeted delivery of imaging probes and therapeutics (Lanza et al, 2019; Zenych et al, 2020) To treat these severe thromboembolic diseases, fibrinolytic agents such as plasmin and plasminogen activators were developed and administered in patients through a systemic approach. Recent research studies have highlighted the success of emerging supramolecular drug delivery systems (DDSs) for their potential theranostic application in a variety of CVDs (Zhang et al, 2017; Bonnard et al, 2019; Disharoon et al, 2019; Yu et al, 2020) Several supramolecular platforms, such as lipid nanoparticles, polymeric nanocarriers, ultrasound-responsive microbubbles, and inorganic. We discuss the rationale behind the choice of activation-specific epitopes and review the challenges of current targeting moieties for the theranostic applications in thrombotic pathologies
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