Combining nanotechnology with current biomedical knowledge for the vascular imaging and treatment of atherosclerosis

Abstract

Activation of vasa vasorum (the microvessels supplying the major arteries) at specific sites in the adventitia initiates their proliferation or 'angiogenesis' concomitant with development of atherosclerotic plaques. Haemorrhagic, leaky blood vessels from unstable plaques proliferate abnormally, are of relatively large calibre but are immature neovessels poorly invested with smooth muscle cells and possess structural weaknesses which may contribute to instability of the plaque by facilitation of inflammatory cell infiltration and haemorrhagic complications. Weak neovascular beds in plaque intima as well as activated adventitial blood vessels are potential targets for molecular imaging and targeted drug therapy, however, the majority of tested, currently available imaging and therapeutic agents have been unsuccessful because of their limited capacity to reach and remain stably within the target tissue or cells in vivo. Nanoparticle technology together with magnetic resonance imaging has allowed the possibility of imaging of neovessels in coronary or carotid plaques, and infusion of nanoparticle suspensions using infusion catheters or implant-based drug delivery represents a novel and potentially much more efficient option for treatment. This review will describe the importance of angiogenesis in mediation of plaque growth and development of plaque instability and go on to investigate the possibility of future design of superparamagnetic/perfluorocarbon-derived nanoparticles for imaging of the vasculature in this disease or which could be directed to the adventitial vasa vasorum or indeed intimal microvessels and which can release active payloads directed against primary key external mitogens and intracellular signalling molecules in endothelial cells responsible for their activation with a view to inhibition of angiogenesis.

Development and applications of photo-triggered theranostic agents

“…These lesions can be present for decades or even throughout a person’s life, presenting as early as infanthood where the early stage lesions consist exclusively of macrophages and T lymphocytes [229]. Instable, dangerous plaques are difficult to diagnose by angiography and plaque rupture accounts for approximately 75% of acute coronary events and 60% of symptomatic carotid artery disease [229, 232]. In atherosclerogenesis, macrophages drive the inflammatory response by secreting cytokines to recruit other cells to lesions as well as produce metalloproteinase which promotes plaque instability [229].…”

Monocyte‐Targeting Supramolecular Micellar Assemblies: A Molecular Diagnostic Tool for Atherosclerosis

“…[14,15] Furthermore, the nanometer size provides favorable pharmacokinetic properties as well as permeability into leaky vasculature that exists in developing disease pathologies in vivo. [16,17] Moreover, monocytes enter plaques from the luminal side of the arterial wall, allowing for accessibility to intravenously delivered particles. In previous work, when the fibrin-targeting peptide, cysteine-arginine-glutamic acid-lysine-alanine (CREKA, previously identified via in vivo phage display), was used as the headgroup, these PAMs localized to microthrombi residing within the shoulder portion of atherosclerotic plaques, a location most prone to rupture, within the well-known murine ApoE knock-out model of atherosclerosis.…”

Nanomedicine in diagnostics and therapy of cardiovascular diseases: beyond atherosclerotic plaque imaging

“…The application of the nanomedical strategies for cardiovascular medicine will have significant impact on the outcomes of atherosclerosis. In cardiovascular medicine, it should provide molecular imaging for the early disease detection [2] , and the region-and target-specific modalities for the therapeutical interventions in advanced disease [3] .…”