Experimental vascular models for evaluation of novel contrast agent nanoparticles

Abstract

Purpose: Nanotechnology is a rapidly growing field with a wide range of applications for nanoparticles in drug delivery and medical imaging. Understanding nanoparticle interactions with living cells and tissues is vital in determining their effectiveness, toxicity, and biodistribution. Methods: Nanoparticles of various types have been investigated in several vascular models to evaluate adhesion, internalization, and biodistribution. Kinetics of particle uptake were assessed in human endothelial cells. A parallel-plate flow chamber (PPFC) was used for endothelial cell culture with control over shear stress. In vivo techniques include zebrafish embryos, the chicken embryo chorioallantoic membrane (CAM) model, and a partial carotid ligation, ApoE knockout murine model of atherosclerosis. Fluorescence correlation spectroscopy was used with the CAM model to monitor particle disappearance from blood over time. MR imaging and fluorescence microscopy were used to assess particle localization. Results: The vascular models employed provided a breadth of detailed knowledge on the potential for nanoparticles to target tissues and attach to cells. As shown with the PPFC and zebrafish, nanoparticle uptake varied greatly with shear stress and flow pattern. The PPFC also allowed examination of the amount of nanoparticle contrast agent needed to cause a change in magnetic resonance signal. The tortuous vessels of the zebrafish caudal tail plexus showed the highest particle uptake, localized to areas with disturbed flow. The CAM model highlighted the importance of particle composition in determining uptake kinetics. Conclusions: Understanding nanoparticle localization in a physiologically-relevant environment is important for determining risk profiles and efficacy for drug delivery or molecular imaging.