Intraperitoneal Injection Improves the Uptake of Nanoparticle-Labeled High-Density Lipoprotein to Atherosclerotic Plaques Compared With Intravenous Injection

Abstract

A therosclerosis remains the main cause of morbidity and mortality in industrialized and developing nations. 1 Growing evidence suggests that the decisive factor determining atherosclerotic plaque vulnerability is the plaque configuration rather than the degree of luminal narrowing. 2Molecular imaging may offer a new diagnostic tool to discriminate stable and vulnerable atherosclerotic plaques at an early stage of disease and to improve the detection of morphological and functional abnormalities within the vessel wall. 3,4 The major hallmarks of early atherosclerotic lesion formation are endothelial dysfunction and accumulation of large amounts of lipoprotein-derived cholesterol esters in macrophages within Background-The aim of this study was to assess whether high-density lipoprotein (HDL) labeled with superparamagnetic iron oxide nanoparticles (SPIOs) and quantum dots was able to detect atherosclerotic lesions in mice after intravenous and intraperitoneal injection by multimodal imaging. Methods and Results-Nanoparticle-labeled HDLs (NP-HDLs) were characterized in vitro by dynamic light scattering and size exclusion chromatography with subsequent cholesterol and fluorescence measurements. For biodistribution and blood clearance studies, NP-HDL SPIOs radiolabeled with 59Fe (NP-HDL 59Fe-SPIOs ) were injected intravenously or intraperitoneally into ApoE knockout mice (n=6), and radioactivity was measured using a gamma counter. NP-HDL accumulation within atherosclerotic plaques in vivo and ex vivo was estimated by MRI at 7 Tesla, ex vivo confocal fluorescence microscopy, x-ray fluorescence microscopy, and histological analysis (n=3). Statistical analyses were performed using a 2-tailed Student t-test. In vitro characterization of NP-HDL confirmed properties similar to endogenous HDL. Blood concentration time curves showed a biexponential decrease for the intravenous injection, whereas a slow increase followed by a steady state was noted for intraperitoneal injection. Radioactivity measurements showed predominant accumulation in the liver and spleen after both application approaches. NP-HDL 59Fe-SPIOs uptake into atherosclerotic plaques increased significantly after intraperitoneal compared with intravenous injection (P<0.01). In vivo MRI showed an increased uptake of NP-HDL into atherosclerotic lesions after intraperitoneal injection, which was confirmed by ex vivo MRI, x-ray fluorescence microscopy, confocal fluorescence microscopy, and histological analysis. Conclusions-In vivo MRI and ex vivo multimodal imaging of atherosclerotic plaque using NP-HDL is feasible, and intraperitoneal application improves the uptake within vessel wall lesions compared with intravenous injection. (Circ Cardiovasc Imaging. 2014;7:303-311.)

Association of the ApoE gene polymorphism and dietary factors with cerebral infarction and circulating lipid concentrations

“…Thus, the hazards of smoking can be partly attributed to its effects on lipoprotein levels (Jung et al, 2014). Smoking was not shown to be associated with gender, age, body mass index, or blood pressure levels; rather, it was associated with the independent factor of lipid metabolism (Jung et al, 2014). In addition, this study also showed that alcohol drinking significantly increased lipid levels.…”

“…This might be due to a variety of compounds in tobacco, including the primary compounds nicotine and carbon monoxide, as animal experimentation has proven that nicotine and carbon monoxide in tobacco may elevate TG levels. Thus, the hazards of smoking can be partly attributed to its effects on lipoprotein levels (Jung et al, 2014). Smoking was not shown to be associated with gender, age, body mass index, or blood pressure levels; rather, it was associated with the independent factor of lipid metabolism (Jung et al, 2014).…”

“…In addition, this study also showed that alcohol drinking significantly increased lipid levels. Long-term intake of high concentrations of alcohol has recently been shown to induce weakened ApoE expression in the mouse liver (Jung et al, 2014). It also had an impact on lipid levels.…”

Nanomedicine for the molecular diagnosis of cardiovascular pathologies

“…Another strategy to enhance plaque penetration is the inclusion of these systems in HDL-like systems for detection of macrophages [36]. Not only SPIO, but also other inorganic compounds, such as gold nanocrystals, were loaded with success in such versatile nanoplatforms [37].…”

Quantitative Activity Measurements of Brown Adipose Tissue at 7 T Magnetic Resonance Imaging After Application of Triglyceride-Rich Lipoprotein 59Fe-Superparamagnetic Iron Oxide Nanoparticle

“…3 By comparing 2 different application approaches (IV vs IP), our goal was to determine whether there is also a temperature-dependent mechanism via which the TRL-59 Fe-SPIOs can exit the peritoneal cavity. Previous studies 12,13 demonstrated that the uptake by the liver and spleen is lower after IP injection of liposomes than after IV injection, resulting in a higher accumulation of liposomes in the region/tissue of interest. The knowledge and accurate description of different application approaches for pharmaceuticals or contrast media (IV vs IP vs intramuscular vs subcutaneous) are of high benefit for imaging as well as for therapeutically studies because different distributions of a contrast agent or a drug can be realized.…”