<p>Polydopamine-modified dual-ligand nanoparticles as highly effective and targeted magnetic resonance/photoacoustic dual-modality thrombus imaging agents</p>

Abstract

Background Platelet activation and subsequent aggregation are the initial stages of thrombosis. A molecular probe that specifically targets activated platelets and remains retained under high shear stress in vivo can enhance the imaging effect to achieve early and accurate diagnosis. Methods and materials In this study, we constructed nanoparticles (NPs) using polydopamine to carry two peptides that simultaneously bind integrin αIIbβ3 and P-selectin on activated platelets to enhance the targeting of NPs to thrombus. Results The targeting specificity and binding stability of the NPs on red and white thrombi were demonstrated in vitro using a simulated circulatory device and the targeting effect of the NPs on mixed thrombus was studied by magnetic resonance (MR)/photoacoustic (PA) dual-modality imaging in vivo. NPs that were surface modified with both peptides have higher selectivity and retention to red and white thrombi in vitro than NPs with a single or no peptide, and the targeting effect was closely related to the number and distribution of activated platelets as well as the structure and type of thrombus. The NPs also have MR/PA dual-modality imaging functionality, significantly enhancing the imaging of mixed thrombus in vivo. Conclusion These dual-targeted NPs have improved targeting specificity and binding stability to different thrombi under high shear stress and are beneficial for the early diagnosis of thrombosis.

Small Dimension—Big Impact! Nanoparticle-Enhanced Non-Invasive and Intravascular Molecular Imaging of Atherosclerosis In Vivo

“…MRI-signal area at the site of induced thrombus decreased significantly as compared to non-targeted control NPs. Subsequent histopathological assessment confirmed localization of DDNPs on thrombus material [40].…”

“…Mainly two considerations mark the difference between scientific curiosity and clinical need with regard to these technologies. [34] (THI0567-lipid NP) liposomal NP bearing gadolinium, selective integrin α4β1 antagonist THI0567 and rhodamine [28] (NAP9-lipid NP) paramagnetic micellar NP conjugated with gadolinium, rhodamine and EMMPRIN-specific binding peptide NAP9 [30] (A5-mNP) micellar NP bearing Cy5.5 and rhodamine, gadolinium and polymers, covalently coupled to phosphatidylserine ligand annexin A5 [36] ( 64 Cu-CANF-comb) NPR-C-targeting polymeric positron-emitting nanoparticle (TAP-SiO2@AuNP) gold NP coated with silicon dioxide linked to a thrombin-activatable fluorescent peptide [39] (DDNP) NP based on paramagnetic iron oxide and Indian ink linked to cRGD-and GA-EWVDV-ligands targeting glycoprotein IIb/IIIa and P-selectin on activated platelets [40].…”

Molecular Imaging and Non-molecular Imaging of Atherosclerotic Plaque Thrombosis

“…Photoacoustic (PA)/Magnetic resonance (MR) dual-modality nanoparticles (PA/MR-NPs) with dual ligands were successfully constructed via the double-emulsion method and the pDA method. PA/MR bimodal nanoparticles have been used to target mixed thrombi under high shear stress in vivo for both imaging and thrombolytic treatment in one example of such a dual-modal platform ( 92 ). These targeted nanoparticles exhibit good thrombus affinity, and passive targeting or surface modifications can be used to achieve appropriate contrast for thrombus imaging or drug delivery in a ligand-specific manner ( 93 ).…”

“…Magnetic resonance imaging of thrombosis (B) . The high MR signal area of thrombi is significantly increased after contrast agent injection in the presence of atherosclerotic plaques Reproduced with permission from Zhang et al ( 92 ). Copyright Int J Nanomedicine (2019).…”

New Span-PEG-composited Fe3O4-CNT as a multifunctional ultrasound contrast agent for inflammation and thrombotic niduses

“…1 The imaging of targeted microbubble ultrasound contrast agents in thrombosis and inammation has attracted increased research attention, and the targeted specicity and binding stability of the contrast agent are benecial for early diagnosis. 2,3 Thrombus formation is a common condition of the cardiovascular system. For example, deep vein thrombosis is oen called a "silent killer" because of the lack of obvious symptoms until the late stage.…”