Targeted Nanocarriers for Imaging and Therapy of Vascular Inflammation

Abstract

Vascular inflammation is a common, complex mechanism involved in pathogenesis of a plethora of disease conditions including ischemia-reperfusion, atherosclerosis, restenosis and stroke. Specific targeting of imaging probes and drugs to endothelial cells in inflammation sites holds promise to improve management of these conditions. Nanocarriers of diverse compositions and geometries, targeted with ligands to endothelial adhesion molecules exposed in inflammation foci are devised for this goal. Imaging modalities that employ these nanoparticle probes include radioisotope imaging, MRI and ultrasound that are translatable from animal to human studies, as well as optical imaging modalities that at the present time are more confined to animal studies. Therapeutic cargoes for these drug delivery systems include diverse anti-inflammatory agents, anti-proliferative drugs for prevention of restenosis, and antioxidants. This article reviews recent advances in the area of image-guided translation of targeted nanocarrier diagnostics and therapeutics in nanomedicine.

Figure 1

Cell adhesion molecule (CAM)-mediated approach to the delivery of diagnostic and/or therapeutic nanoparticles to injured vascular endothelium in early inflammation. (A) Leukocyte adhesion and transmigration mediated by CAMs resulting in propagation of inflammation; (B) Imaging or therapy of vascular sites of early inflammation via delivery of CAM-targeted nanoparticles.

Figure 2

Schematic representation of targeted nanoparticles engineered for biomedical imaging and therapeutic drug delivery applications. The components of a multifunctional nanocarrier can include a ligand for cellular targeting, and an encapsulated payload for delivery of the therapeutic agents. The imaging components (e.g. radioisotope, NIR dye) can be incorporated in the interior payload, on the targeting ligand or associated with the nanoparticle shell, for example.

Figure 3

Classes of nanoparticles for imaging and drug delivery, including their size and composition.

Figure 4

(A) Preparation of 200 nm Ab-coated polymeric latex NPs for ⁶⁴Cu PET imaging. ⁶⁴Cu was chelated to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) preconjugated to IgG, and then mixed with unlabeled anti-ICAM or IgG Ab (1:9) for adsorption onto NP surface (~250 Ab/NP). (B) MicroCT (coronal slice) and (C) microPET (coronal slice) images of 2 naïve mice (−LPS) injected with ICAM-targeted NPs or control IgG-coated NPs 1 h p.i. (D) Representative decay-corrected transverse micro-PET images of naïve mice (−LPS) and LPS-challenged mice (+LPS) at 1, 4, and 24 h after NP administration. Uptake intensity map is normalized to the highest pixels in the LPS-challenged mice. Figure modified from [75]. © 2008 Society of Nuclear Medicine.