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Gold Nanorods as Absorption Contrast Agents for Noninvasive Detection of Cancer and Arterial Vascular Disorders . Dr. Rinat Ankri and Dr . Dror Fixler Faculty of Engineering and the Institute of Nanotechnology and Advanced Materials, Bar- Ilan University, Israe l. Specular. Diffuse.
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Gold Nanorods as Absorption Contrast Agents for Noninvasive Detection of Cancer and Arterial Vascular Disorders Dr. RinatAnkriand Dr. DrorFixler Faculty of Engineering and the Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Israel
Specular Diffuse Reflection Reflection Light Interaction with a Turbid Medium Input Scattering Absorption Direct Transmission Diffuse Transmission
Light Path in Irradiated Tissues- The Diffusion Theory Where: Thus, the diffusion reflection (DR) intensity depends on µa and µs’: m= ? Where: ρ= light source-detector distance m = 1 or 2 Schmitt et al., 1990
Digital Scope PDInput Optical fiber 250 µm per step 650 nm PDOutput PD The experimental set-up Fiber Optic Detector 1mm Sample 250 µm per step
The Diffusion Theory; m=1 Simulation Expected µs’=1.6 mm-1* Experimental µs’~2.8 mm-1 Experiments * Cubeddu et.al., 1993
The Diffusion Theory; m=2 Expected µs’=1.6 mm-1* * Cubeddu et.al., 1993 m= 2 ! Simulation Experimental µs’~1.5 mm-1 Experiments Ankri et.al, The Open Optics Journal, 2011
The Vision “Fantastic Voyage” Isaac Asimov (1966)
TEM FAAS CT
The Concept Hand with Ring (Wilhelm Röntgen,1895)
When a nanoparticle is much smaller than the wave length of light, coherent oscillation of the conduction band electrons induced by interaction with an electromagnetic field. This resonance is called Surface Plasmon Resonance (SPR). Figure: Schematic of plasmon oscillation for a sphere, showing the displacement of the conduction electron charge cloud relative to the nuclei. Surface plasmon resonance
W L Aspect Ratio (AR) = L/W Gold nanorodshave shape and size-dependent optical properties originating from anisotropic shapeand tunable aspect ratio. Optical Properties of Gold Nanorods Nikoobakht et al. Chem Mater. 2003, 15,1957-1962.
Under electromagnetic field of light,the conduction band electrons undergo acollective coherent oscillationin resonance with the frequency of the incident light. This is known as the localized surface plasmon resonance (LSPR). Due to their anisotropic shape,2 extinction peaks can be observed from gold nanorods. Gold Nanorods Huang et al. Adv Mater. 2009,21,4880-4910.
A new method for cancer detection based on diffusion reflection measurements of targeted gold nanorods GNR (25 x 65 nm) UV-Vis absorption spectra (normalized) and TEM image
Au Au Head & Neck Cancer Cell
Tumor detection based on DR measurements of targeted gold nanorods (GNR) 650 nm Enhancing the tumor absorption coefficient by EFGR labeled GNR injection. Tumorµa Diffusion Reflection measurements 650 nm
Diffusion reflection decreases faster due to GNRs accumulation 6 6 GNRs injection -6 -6 6 6
Tumor detection based on DR of targeted gold nanorods (GNR) The tumor presents a slope different from the normal tissue’s slope even more than 20 hours post injection. Ankri et.al; A new method for cancer detection based on diffusion reflection measurements of targeted gold nanorods, International journal of Nanomedicine, 2012
Different absorption coefficients GNR exntinction coefficient 1 ml/mg*mm
Calculating tumor GNR concentration from the DR profile in-vivo GNR conc. in tumor = FAA spectroscopy EGFR-targeted Ankri et.al; In-vivo tumor detection using diffusion reflection measurements of targeted gold nanorods- a quantitative study, Journal of Biophotonics, 2012
DR measurements of high concentrations of GNR- a Red shift is observed Dark field Microscopy: GNR with different densities
DR measurements of tumor bearing mice with different concentrations of targeted GNR- a spectral broadening is observed ∆λ λ0 Ankri et.al; Intercoupling surface plasmon resonance and diffusion reflection measurements for real-time cancer detection, Journal of Biophotonics, 2012
NEJM Dec 2013 The Aim: To develop a new, easy to use, and non-invasive method at low cost, to locate atherosclerotic vascular disease at its early stages, particularly unstable plaques with ongoing inflammation prone to rupture
Stable vs. Unstable (vulnerable) Plaques Rich in macrophages, foam cells, inflammatory cells, thin fibrous cap Rich in extracellular matrix smooth muscle cells, thick cap
Macrophages before incubation with GNRs Macrophages+ GNRs 0.02 mg/ml Macrophages+ GNRs 0.2 mg/ml
Homogenous and GNRs • Macrophages +/-GNRs
A cross-section of a rat balloon-injured carotid artery 2 weeks post-injury stained withhematoxylin and eosin (H&E) clearly depicts cellular-rich neointima development.Magnification is 100x for the large photomicrograph. A right carotid artery B left injured carotid artery In Vivo ; Rat injury MODEL