The importance of computed tomography (CT) as one of the leading radiology technologies applied in the field of biomedical imaging escalated the development of nanoparticles as the next generation CT contrast agents. Nanoparticles are expected to play a major role in the future of medical diagnostics due to their many advantages over the conventional contrast agents, such as prolonged blood circulation time, controlled biological clearance pathways and specific molecular targeting capabilities. This paper will describe the basic design principles of nanoparticle-based CT contrast agents and review the state-of-the-art developments and clinical applications of blood pool, passive and active targeting CT contrast agents.
These findings promote the optimization of nanovehicles for transport of drugs through the BBB. The insulin coating of the particles enabled targeting of specific brain regions, suggesting the potential use of INS-GNPs for delivery of various treatments for brain-related disorders.
A critical problem in the treatment of neurodegenerative disorders and diseases, such as Alzheimer's and Parkinson's, is the incapability to overcome the restrictive mechanism of the blood-brain barrier (BBB) and to deliver important therapeutic agents to the brain. During the last decade, nanoparticles have gained attention as promising drug delivery agents that can transport across the BBB and increase the uptake of appropriate drugs in the brain. In this study we have developed insulin-targeted gold nanoparticles (INS-GNPs) and investigated quantitatively the amount of INS-GNPs that cross the BBB by the receptor-mediated endocytosis process. For this purpose, INS-GNPs and control GNPs were injected into the tail vein of male BALB/c mice. Major organs were then extracted and a blood sample was taken from the mice, and thereafter analyzed for gold content by flame atomic absorption spectroscopy. Results show that two hours post-intravenous injection, the amount of INS-GNPs found in mouse brains is over 5 times greater than that of the control, untargeted GNPs. Results of further experimentation on a rat model show that INS-GNPs can also serve as CT contrast agents to highlight specific brain regions in which they accumulate. Due to the fact that they can overcome the restrictive mechanism of the BBB, this approach could be a potentially valuable tool, helping to confront the great challenge of delivering important imaging and therapeutic agents to the brain for detection and treatment of neurodegenerative disorders and diseases.
BackgroundDuring the last decade nanoparticles have gained attention as promising drug delivery agents that can transport through the blood brain barrier. Recently, several studies have demonstrated that specifically targeted nanoparticles which carry a large payload of therapeutic agents can effectively enhance therapeutic agent delivery to the brain. However, it is difficult to draw definite design principles across these studies, owing to the differences in material, size, shape and targeting agents of the nanoparticles. Therefore, the main objective of this study is to develop general design principles that link the size of the nanoparticle with the probability to cross the blood brain barrier. Specifically, we investigate the effect of the nanoparticle size on the probability of barbiturate coated GNPs to cross the blood brain barrier by using bEnd.3 brain endothelial cells as an in vitro blood brain barrier model.ResultsThe results show that GNPs of size 70 nm are optimal for the maximum amount of gold within the brain cells, and that 20 nm GNPs are the optimal size for maximum free surface area.ConclusionsThese findings can help understand the effect of particle size on the ability to cross the blood brain barrier through the endothelial cell model, and design nanoparticles for brain imaging/therapy contrast agents.
Gold nanoparticles have emerged as some of the most extensively utilized nanoplatforms for the diagnosis, imaging, monitoring and treatment of malignant diseases. In particular, in computed tomography (CT) imaging and in therapy (PTT), the exploitation of the various, advantageous properties of gold nanoparticles have resulted in numerous advances in each of these fields. The purpose of this review is to assess the status of gold-nanoparticle mediated CT and PTT, highlight several promising outcomes and motivate the combination of these two functionalities in the same nanoparticle platform. The given examples of research based advances and the encouraging results of in vitro and in vivo studies provide much excitement and promise for future theranostic (therapy + diagnostic) clinical applications, as well as for image-guided therapy and/or surgery, and their monitoring.
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