Multimodal Nanoagents for the Detection of Intravascular Thrombi

Abstract

Thrombosis underlies numerous life-threatening cardiovascular syndromes. Development of thrombosis-specific molecular imaging agents to detect and monitor thrombogenesis and fibrinolysis in vivo could improve the diagnosis, risk stratification, and treatment of thrombosis syndromes. To this end, we have synthesized efficient multimodal nanoagents targeted to two different constituents of thrombi, namely, fibrin and activated factor XIII. These agents are targeted via the conjugation of peptide-targeting ligands to the surface of fluorescently labeled magnetic nanoparticles. As demonstrated by in vitro and in vivo studies, both nanoagents possess high affinities for thrombi, and enable mutimodal fluorescence and magnetic resonance imaging.

From Molecular Imaging to Pathogenesis and Vice Versa…

“…This is especially relevant for detecting the older thrombi with lower fibrin content. 12 Besides fibrin, FXIIIa [19][20][21][22][23][24][25] and thrombin 26,27 have been evaluated as targets for thrombus imaging in the preclinical studies ( Figure). Thrombin and FXIIIa are important factors in the coagulation cascade, and probes targeting these molecules promise to be excellent research tools for elucidation of the temporal roles of these factors in vivo.…”

Fe₃O₄-based PLGA nanoparticles as MR contrast agents for the detection of thrombosis

“…A variety of particles have been reported in the literature for thrombosis detection. [4][5][6][7][8][9][10][11][12][13][14][15][16][17] Compared with ultrasound, [4][5][6][7][8] nuclear medicine, 9,10,18 and computed tomography (CT), 11 the advantages of magnetic resonance imaging (MRI) that are particularly relevant in the context of cardiovascular diseases are its high temporal and spatial imaging resolution, high soft tissue contrast,…”

“…In recent years, MR contrast agents, such as gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA), superparamagnetic iron oxide (SPIO), and ultra-small superparamagnetic particles of iron oxide (USPIOs), have been successfully encapsulated into macromolecular polymer particles to create novel contrast agents. [12][13][14][15][16][17] The fibrin-targeted MR molecular probe EP-2104R has entered clinical trials with encouraging results. 19 Comparatively Gd-DTPA, SPIO and USPIO have the advantages of long half-lives, high relaxation rates, and minimal side effects.…”

“…20,21 Most previous studies of thrombosis detection molecules have focused on their physicochemical properties in vitro and targeting abilities in vivo. 12,15 In some studies, new MRI contrast agents targeting activated platelets have been successfully prepared and used to detect endovascular thrombi in vivo. 17,22,23 Similarly, in our previous studies, we synthesized novel types of thrombus-targeting particles and confirmed their targeting ability and contrast-enhancing effects in vitro.…”

Preparation and characterization of gadolinium-loaded PLGA particles surface modified with RGDS for the detection of thrombus

“…To date, numerous studies have been focused on the design of MR probes with high relaxation efficiency to improve MR thrombus depiction. [4][5][6][7][8][9] However, such probes are becoming more and more complicated, are not readily available for other researchers, and are not yet approved for clinical applications. In this study, we introduce a relatively simple method to prepare an MR probe for targeting activated platelets.…”