Synthesizing nanovectors that avoid immune clearance and thus possess increased circulation time is challenging since particles are typically quickly removed from the bloodstream. Approaches such as PEGylation and varying the size, shape, and composition of nanovectors may be explored to achieve this goal. Cardiovascular Targets Recent technologies have focused on discovering Inhibitors,research,lifescience,medical appropriate molecules to target for CVDs once the particle approaches the vessel wall. The vascular endothelium
that lines blood vessels and creates a natural barrier separating blood from surrounding tissue is considered an attractive target for both drug delivery and imaging due to its proximity to intravenously administered therapy. Additionally, the unique ABT-199 manufacturer markers expressed by endothelial cells during the progression of CAD offer an opportunity
for the Inhibitors,research,lifescience,medical design of molecular imaging probes and targeted nanovectors for localized treatments. Proinflammatory markers such as selectins, VCAM-1, and ICAM-1 expressed during chronic inflammation, which is prominent in most CVDs, serve as prime targets for targeted nanovectors.13 Another means of directing nanovectors to CAD is to target fibrin clots formed at the site of atherosclerosis when blood comes into contact with exposed tissue within the plaque.14 While nanovectors may be targeted to biomarkers expressed by the endothelium, Inhibitors,research,lifescience,medical the endothelial cells themselves may not be the intended target of therapeutic action. For example, cells such as monocytes, T cells, and foam cells that are recruited into atherosclerotic plaques or the underlying tissue have served as targets.15 When the final destination of imaging and drug carriers Inhibitors,research,lifescience,medical is not the vascular endothelium but rather the underlying tissue/organ, particle internalization and/or transcytosis of the nanovector must
be considered.16 17 Another possible approach for treating atherosclerosis could rely on targeting neovascularization of the vasa vasorum (network of small arteries Inhibitors,research,lifescience,medical in the vascular wall) that is strongly correlated with plaque growth and rupture.18 Particle Type Particle material and fabrication technique are important design parameters that affect the performance of nanovectors. Several types of carriers have been proposed for use in the treatment and imaging of cardiovascular diseases including soluble Urease carriers, viral carriers, lipid-based carriers, nano/microbubbles, polymeric, and inorganic-based nanocarriers (Figure 1). Figure 1. Schematic of (A) soluble, (B) polymer-based, and (C) lipid-based nanovectors. Soluble carriers include modified plasma proteins such as albumin, antibodies, and soluble biopolymers such as dextran and chitosan, and the design is such that the active agent is covalently linked to the carrier. For example, albumin has been conjugated to gadolinium for use as an MRI contrast agent.