In Vivo Targeting and Imaging of Atherosclerosis Using Multifunctional Virus-Like Particles of Simian Virus 40

Abstract

Atherosclerosis is a leading cause of death globally. Targeted imaging and therapeutics are desirable for the detection and treatment of the disease. In this study, we developed trifunctional Simian virus 40 (SV40)-based nanoparticles for in vivo targeting and imaging of atherosclerotic plaques. These novel trifunctional SV40-based nanoparticles encapsulate near-infrared quantum dots and bear a targeting element and a drug component. Using trifunctional SV40-based nanoparticles, we were able to noninvasively fluorescently image atherosclerotic plaques in live intact ApoE(-/-) mice. Near-infrared quantum dots encapsulated in the SV40 virus-like particles showed prominent optical properties for in vivo imaging. When different targeting peptides for vascular cell adhesion molecule-1, macrophages, and fibrin were used, early, developmental, and late stages of atherosclerosis could be targeted and imaged in live intact ApoE(-/-) mice, respectively. Targeted SV40 virus-like particles also delivered an increased concentration of the anticoagulant drug Hirulog to atherosclerosis plaques. Our study provides novel SV40-based nanoparticles with multivalency and multifunctionality suitable for in vivo imaging, molecular targeting, and drug delivery in atherosclerosis.

Recent Advances in Managing Atherosclerosis via Nanomedicine

“…injection of tri‐functional Simian virus 40 (SV40)‐based NPs (FH‐QDs), which contain quantum dots, fibrin‐targeting peptides, and the thrombin inhibitor hirulog. Reproduced with permission . Copyright 2016, American Chemical Society.…”

“…In 2013, Marrache and Dhar prepared synthetic HDL‐based NPs that contain apolipoprotein‐mimetic peptides for targeting the plaque, quantum dots for NIRF imaging, and triphenylphosphonium cations for detecting collapse in mitochondrial membrane potential . In 2016, Sun et al engineered Simian virus 40 (SV40)‐based NPs containing NIRF‐emitting quantum dots, fibrin‐targeting peptides, and hirulog anticoagulant molecules (Figure C). By encapsulating quantum dots inside SV40‐based NPs, the authors achieved higher brightness, photostability, and detection sensitivity in deep tissues than using unmodified quantum dots.…”

“…They also detected reduced necrotic areas and oxidative stress levels in the brachiocephalic artery, a typical location of advanced necrotic plaques. In 2016, Sun et al applied Simian virus NPs to deliver hirulog peptides to the atherosclerotic plaque and reported high‐antithrombin activity in the aorta. Yet, they did not provide strong evidence on the anti‐atherosclerosis efficacy of these NPs, such as reduced areas of plaques, counts of infiltrated immune cells, and expression of inflammatory markers.…”

Virus-like nanoparticles: Emerging Tools for Targeted Cancer Diagnostics and Therapeutics

“…Requiring more extensive bioengineering, the encapsidation of guest proteins is an exciting area with applications in advanced vaccine design [13], cytotoxic protein delivery [14] and genome editing [15]. Encapsidation of inorganic cargos such as quantum dots [16] and metallic cores offer opportunities in molecular imaging. A range of MRI and positron emission tomography agents have also been delivered by VLNPs [17].…”

“…It follows that the encapsidation of therapeutic or diagnostic cargos can be, and has been, combined with external functionalization in some of the examples previously mentioned [5,8,10,11,14,16]. The flexibility afforded by some VLNPs for dual modification means that both genetic and chemical modifications can be combined to create sophisticated, targeted nanoparticle delivery vehicles.…”