Magnetic Targeting Improves the Therapeutic Efficacy of Microbubble-Mediated Obstructive Thrombus Sonothrombolysis

Abstract

Background Magnetic targeting may help microbubbles (MBs) reach obstructive thrombi and improve the efficacy of MB-mediated sonothrombolysis, but the role of magnetic targeting in MB-mediated sonothrombolysis remains elusive. Objectives We investigate the feasibility and efficacy of magnetically targeted MB-mediated sonothrombolysis for the treatment of obstructive thrombi. Materials and Methods Red and white thromboembolic models were established in vitro and in vivo. The models were randomly assigned to the control, ultrasound plus control MB (US + C-MB), ultrasound plus magnetic MB (US + M-MB), or US + M-MB + recombinant tissue-type plasminogen activator (r-tPA) groups and treated for 30 minutes. The recanalization rate, average blood flow velocity, hindlimb perfusion, and skeletal muscle injury marker levels were recorded. Results The recanalization rate, average blood flow velocity, and hindlimb perfusion in the red and white thromboembolic models were all significantly higher in the US + M-MB and US + M-MB + r-tPA groups than in the control and US + C-MB groups both in vitro and in vivo. Moreover, the levels of the skeletal muscle injury markers were all significantly lower in the US + M-MB and US + M-MB + r-tPA groups than in the other two groups in vivo for both thromboembolic models. However, the thrombolytic effects of red thrombi performed better than those of white thrombi in the US + M-MB + r-tPA group. Conclusion M-MB-mediated sonothrombolysis improves the efficacy of thrombolysis both in vitro and in vivo, and reduces tissue damage in clogging model; thus, this method may serve as a promising approach for treating thrombus-occlusive diseases.

Progress in Stimuli‐Responsive Biomaterials for Treating Cardiovascular and Cerebrovascular Diseases

“…[167] In this approach, an external magnetic field guides the magnetic nanoparticles in different body organs. As an example, magnetic nanovesicles (MNVs) that were formed from mesenchymal stem cells (MSCs) encapsulating iron oxide Ultrasound-mediated clots' lysis in vitro and in vivo (iliac arteries) using magnetic microbubbles [151] Ultrasound Fe 3 O 4 -PLGA-PFH-CREKA 4 mg kg −1 of NPs Ultrasound-assisted thrombolysis [152] Light EM-JPM made of chitosan/heparin NPs ≈ 4.9 × 10 5 /µL (50 µL vol) Light-induced localized hyperthermia [153] Light PMSF−DyLight-DBCO bioengineered cells inside a hydrogel N/A Light-mediated controlled production of uPA in situ through the activation of TRPV1 ion channel [154] Light Tet@Au@MSNs uPA/500 µg mL −1 (in vitro) N/A (in vivo)…”

“…The rationale behind the use of ultrasound is the mechanical lysis of the thrombi due to the bursting of biomaterials responsive to ultrasounds (e.g., microbubbles). Based on this, magnetic microbubbles [ 151 ] and or ultrasound responsive droplets [ 152 ] have been considered as mechanical thrombolytic approaches. In the first case, the fabricated magnetic microbubbles were guided with the help of an external magnetic field to the thrombus area, where the ultrasound‐mediated release of tPA and the bursting of the bubbles led to clot lysis.…”

“…The rationale behind the use of ultrasound is the mechanical lysis of the thrombi due to the bursting of biomaterials responsive to ultrasounds (e.g., microbubbles). Based on this, magnetic microbubbles [151] and or ultrasound responsive droplets [152] have been considered as mechanical thrombolytic approaches. In the first case, the fabricated magnetic…”

Cetuximab-Conjugated Perfluorohexane/Gold Nanoparticles for Low Intensity Focused Ultrasound Diagnosis Ablation of Thyroid Cancer Treatment

“…In addition, studies in histology andimmunohistochemistry were conducted. Sections of the tissue werestained with histophalogy [48][49][50].…”

Nanodroplet‐Coated Microbubbles Used in Sonothrombolysis with Two‐Step Cavitation Strategy

“…[12][13][14] Cavitation of microbubbles, irritated by ultrasound, can induce sono pores, but it only stays on the surface of thrombus. [15] Magnetic particles, [16][17][18] nanoparticles, [19][20][21] and nanodroplets [22][23][24] are also used in treatment of thrombosis because nanoparticles can enter thrombus more easily due to their small size. [15,25] Recent analysis shows that the delivery of nanoparticles into thrombus is still difficult because the central core of thrombus is filled with densely packed fibrin and activated platelets, which seriously hinders the deep diffusion of nanoparticles.…”