Ultrasound Microbubble Delivery Targeting Intraplaque Neovascularization Inhibits Atherosclerotic Plaque in an APOE-deficient Mouse Model

Abstract

UTMD targeting intraplaque neovascularization was found to inhibit atherosclerotic plaque in a mouse model of atherosclerosis, suggesting the potential of microbubble-mediated ultrasound technology in aiding drug delivery for atherosclerosis treatment.

Anti-inflammatory and Anti-thrombotic Efficacy of Targeted Ultrasound Microbubbles on LPS-induced HUVEC Cells

“…In conclusion, this is the first demonstration of antiinflammatory efficacy of targeted microbubbles on an earlystage AS model in vitro. In combination with our previous in vivo experiment (6), we believe that UTMD therapy has clinical potential for AS treatment.…”

“…We previously reported that treatment with UTMD targeting Endostar and ICAM-1 inhibited atherosclerotic plaques in animal models (6). Endostar is a modified version of recombinant human endostatin, which is a strong inhibitor of angiogenesis (22) and plaque neovascularization (23).…”

“…In our previous study, we reported the inhibitory effect of an ultrasound-targeted microbubble delivery (UTMD) therapy in an atherosclerotic APOE-deficient mouse model. The drug-loaded microbubbles (MBs) targeted intraplaque neovascularization by conjugating microbubbles with an angiogenesis inhibitor Endostar and an antibody against ICAM-1 (intercellular adhesion molecule-1) and inhibited the formation of atherosclerotic plaque in vivo (6).…”

Ultrasound-Responsive Cavitation Nuclei for Therapy and Drug Delivery

“…In cardiovascular drug delivery, cavitation nuclei are co-administered or loaded with different therapeutics for the treatment of various diseases. For atherosclerosis treatment in an ApoE-deficient mouse model, intercellular adhesion molecule-1-targeted microbubbles carrying the angiogenesis inhibitor Endostar were used (Yuan et al 2018). Upon intermittent insonification over the abdominal and thoracic cavity with 1 MHz ultrasound (2 W/cm 2 intensity, 50% duty cycle) for 30 s with two repeats and another treatment 48 h later, plaque area and intraplaque neovascularization were significantly reduced 2 wk after treatment.…”

Using Acoustic Fields to Fabricate ECM-Based Biomaterials for Regenerative Medicine Applications

“…The development of novel techniques to enhance the susceptibility of biological systems to acoustic effects has expanded the versatility of ultrasound across both diagnostic and therapeutic domains. In particular, advances in microbubble chemistry have enabled the use of acoustically-responsive droplets as vehicles for the delivery of drugs, including recombinant proteins [ 135 ], small molecules [ 136 ], and genetic material [ 137 ]. In these systems, which vary among applications in their composition and preparation, a therapeutic payload is suspended in a cavitation-sensitive material, often gas or perfluorocarbons, and encapsulated within a stabilizing shell [ 138 ].…”