Targeted Diagnosis, Therapeutic Monitoring, and Assessment of Atherosclerosis Based on Mesoporous Silica Nanoparticles Coated with cRGD-Platelets

Abstract

Objective. The off-target effects and severe side effects of PPARα and LXRα agonists greatly limit their application in atherosclerosis (AS). Therefore, this study intended to use mesoporous silica nanoparticles as carriers to generate MnO nanoparticles in situ with T1WI-MRI in mesoporous pores and simultaneously load PPARα and LXRα agonists. Afterward, cRGD-chelated platelet membranes can be used for coating to construct a new nanotheranostic agent. Methods. cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles were synthesized by a chemical method. Dynamic light scattering (DLS) was utilized to detect the size distribution and polydispersity index (PDI) of the nanoparticles. The safety of the nanoparticles was detected by CCK8 in vitro and HE staining and kidney function in vivo. Cell apoptosis was detected by flow cytometry detection and TUNEL staining. Oxidative stress responses (ROS, SOD, MDA, and NOX levels) were tested via a DCFH-DA assay and commercial kits. Immunofluorescence and phagocytosis experiments were used to detect the targeting of nanoparticles. Magnetic resonance imaging (MRI) was used to detect the imaging performance of cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles. Using western blotting, the expression changes in LXRα and ABCA1 were identified. Results. cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles were successfully established, with a particle size of approximately 150 nm and PDI less than 0.3, and showed high safety both in vitro and in vivo. cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles showed good targeting properties and better MRI imaging performance in AS. cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles showed better antioxidative capacities, MRI imaging performance, and diagnostic and therapeutic effects on AS by regulating the expression of LXRα and ABCA1. Conclusion. In the present study, cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles with high safety and the capacity to target vulnerable plaques of AS were successfully established. They showed better performance on MRI images and treatment effects on AS by promoting cholesterol efflux through the regulation of ABCA1. These findings might address the problems of off-target effects and side effects of nanoparticle-mediated drug delivery, which will enhance the efficiency of AS treatment and provide new ideas for the clinical treatment of AS.

Targeting macrophages in atherosclerosis using nanocarriers loaded with liver X receptor agonists: A narrow review

“…A recent study reported a new nanoparticle, which uses mesoporous silica nanoparticles as carriers to generate nanoparticles that are simultaneously loaded with peroxisome proliferators-activated receptor alpha and LXRα agonists. These novel nanoparticles successfully reduce atherosclerotic plaque area in rats (Zhang W et al, 2022). It has been demonstrated that modification of nanoparticles with platelet membranes can significantly enhance the targeting property of nanocarriers .…”

“…Although the first line lipid-lowering drugs, statins, are capable of lowering LDL cholesterol (LDL-C) and suppress inflammation, these drugs can only reduce ~30% cardiovascular disease (CVD) events. Furthermore, clinical studies have found various side effects of statin therapy (Qiao et al, 2022;Zhang W et al, 2022). A promising alternative to statin therapy is the inhibition of the proprotein convertase subtilisin/kexin-9 type, thereby increasing the uptake of circulating LDL particles by the liver (Qiao et al, 2022).…”

Nanomedicine for Diagnosis and Treatment of Atherosclerosis

“…Afterward, the research scope extended from traditional drugs to various small molecule regulators, proteins, cytokines, and gene components. Besides, nanocarriers have gradually expanded to liposomes, [ 198 ] biomimetic nanomaterials, [ 199 ] polymers, [ 26a ] micelles, [ 200 ] mesoporous structures, [ 201 ] and metal‐organic framework (MOFs). [ 202 ]…”

“…However, the surfaces or interiors of nanomaterials can easily couple with various components, making it possible to undergo treatment under imaging guidance or real‐time monitoring during treatment. [ 26 ] This undoubtedly promotes ever‐greater advances and offers unprecedented solutions for disease exploration.…”

M2 Macrophage Membrane‐Camouflaged Fe3O4‐Cy7 Nanoparticles with Reduced Immunogenicity for Targeted NIR/MR Imaging of Atherosclerosis

“…[28,29] However, there are several complex specific targets in AS, including CC-motif chemofactor ligand 2 (CCL2) and CD68 in inflamed macrophages, [30,31] ICAM 1 and VCAM 1 in inflamed endothelial cells, [32] and MMP-9 and KLF4 within inflamed smooth muscle cells. [33] Various studies have focused on a single target, [34] whereas very few have focused on multiple targets. Therefore, focusing on numerous targets as atherosclerotic markers is essential to assess nanoparticle imaging comprehensively.…”