Gold nanoparticles as high-resolution X-ray imaging contrast agents for the analysis of tumor-related micro-vasculature

Abstract

BackgroundAngiogenesis is widely investigated in conjunction with cancer development, in particular because of the possibility of early stage detection and of new therapeutic strategies. However, such studies are negatively affected by the limitations of imaging techniques in the detection of microscopic blood vessels (diameter 3-5 μm) grown under angiogenic stress. We report that synchrotron-based X-ray imaging techniques with very high spatial resolution can overcome this obstacle, provided that suitable contrast agents are used.ResultsWe tested different contrast agents based on gold nanoparticles (AuNPs) for the detection of cancer-related angiogenesis by synchrotron microradiology, microtomography and high resolution X-ray microscopy. Among them only bare-AuNPs in conjunction with heparin injection provided sufficient contrast to allow in vivo detection of small capillary species (the smallest measured lumen diameters were 3-5 μm). The detected vessel density was 3-7 times higher than with other nanoparticles. We also found that bare-AuNPs with heparin allows detecting symptoms of local extravascular nanoparticle diffusion in tumor areas where capillary leakage appeared.ConclusionsAlthough high-Z AuNPs are natural candidates as radiology contrast agents, their success is not guaranteed, in particular when targeting very small blood vessels in tumor-related angiography. We found that AuNPs injected with heparin produced the contrast level needed to reveal--for the first time by X-ray imaging--tumor microvessels with 3-5 μm diameter as well as extravascular diffusion due to basal membrane defenestration. These results open the interesting possibility of functional imaging of the tumor microvasculature, of its development and organization, as well as of the effects of anti-angiogenic drugs.

Effects of iron oxide nanoparticles on biological responses and MR imaging properties in human mammary healthy and breast cancer epithelial cells

“…[15][16][17][18][19] Nanoparticles can extravasate from the leaky tumor vessels and accumulate in tumor tissues. 20,21 However, the uptake and cellular response of solid tumor cells to USPIONs has not been clearly investigated. As a result, the goals of the present study were to determine whether: (1) breast cancer cells have increased nanoparticle uptake compared to normal cells, (2) nanoparticle size and surface coating affects the uptake and cellular responses of the particles, (3) nanoparticles cause toxicity to normal and breast cancer cells, and (4) if there are any differences in MRI contrast resulting from differential uptake in breast cancer cells compared to normal cells.…”

What Can Nanomedicine Learn from the Current Developments of Nanotechnology?

“…The main focus of using nanomedical imaging technology currently is in cancer detection. Recently Chien et al reported that administration of gold nanoparticle together with heparin produced contrast in X-ray imaging which was suffi cient to see tumour microvessel (3-5 μm diameter) or extravascular diffusion [ 40 ]. For MRI contrast agents, the use of iron oxide nanoparticles is a classic example.…”

Applications of gold nanoparticles in medicine and therapy

“…In 2012, Chien et al 156 used AuNPs as high-resolution X-ray imaging contrast agents for analysis of tumor-related micro-vasculature. 156 AuNMs hold great interest in imaging field thanks to their characteristics such as mono dispersity, stability, minimal toxicity and excellent contrasting for transmission electron microscopy (TEM) analysis, which enable tracking with unprecedented resolution on dynamic of uptake, intracellular sorting and potential secretion. 157,158 Figure 8 Scheme of the developed method for detection of DNA methylation and assay of DNA methyltransferase activity.…”