[Retracted] 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 PPAR α and LXR α 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 PPAR α and LXR α agonists. Afterward, cRGD‐chelated platelet membranes can be used for coating to construct a new nanotheranostic agent. Methods . cRGD‐platelet@MnO/MSN@PPAR α /LXR α 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@PPAR α /LXR α nanoparticles. Using western blotting, the expression changes in LXR α and ABCA1 were identified. Results. cRGD‐platelet@MnO/MSN@PPAR α /LXR α 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@PPAR α /LXR α nanoparticles showed good targeting properties and better MRI imaging performance in AS. cRGD‐platelet@MnO/MSN@PPAR α /LXR α nanoparticles showed better antioxidative capacities, MRI imaging performance, and diagnostic and therapeutic effects on AS by regulating the expression of LXR α and ABCA1. Conclusion. In the present study, cRGD‐platelet@MnO/MSN@PPAR α /LXR α 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.

Topics & Concepts