Highly purified biocompatible gold nanorods for contrasted optoacoustic imaging of small animal models (original) (raw)
Related papers
2011
We report on the optoacoustic (OA) imaging of the whole mouse body using a biocompatible contrast agent - highly purified, pegylated gold nanorods (GNR) - which has strong optical absorption in the near-infrared region and low level of toxicity. In vitro toxicity studies showed no significant change in survival rates of the cultured normal epithelium IEC-6 cells when incubated for 24 hours with up to 1 nM of GNR. In vivo toxicity studies in nude mice showed no pathological changes in liver 1 month after the IV injection of GNR with intra-body concentration around 0.25-0.50 nM. In order to study the enhancement of the OA contrast and accumulation of GNR in different tissues, we performed 3D OA imaging of live nude mice with IV-injected GNR. The enhancement of the OA contrast in comparison with the images of the untreated mice was visible starting 1 hour after the GNR injection. The OA contrast of kidneys, liver, and spleen peaked at about 2-3 days after the administration of the GNR, and then was gradually reducing.
Molecular Imaging III, 2011
We report on the optoacoustic (OA) imaging of the whole mouse body using a biocompatible contrast agent -highly purified, pegylated gold nanorods (GNR) -which has strong optical absorption in the near-infrared region and low level of toxicity. In vitro toxicity studies showed no significant change in survival rates of the cultured normal epithelium IEC-6 cells when incubated for 24 hours with up to 1 nM of GNR. In vivo toxicity studies in nude mice showed no pathological changes in liver 1 month after the IV injection of GNR with intra-body concentration around 0.25-0.50 nM. In order to study the enhancement of the OA contrast and accumulation of GNR in different tissues, we performed 3D OA imaging of live nude mice with IV-injected GNR. The enhancement of the OA contrast in comparison with the images of the untreated mice was visible starting 1 hour after the GNR injection. The OA contrast of kidneys, liver, and spleen peaked at about 2-3 days after the administration of the GNR, and then was gradually reducing.
2011
We used a three-dimensional optical tomogaphy system that was previously developed to create high contrast maps of optical absorbance of mice tissues. In this study, animals were scanned before and after injection of gold nanorods (GNRs) at different time periods. As-synthesized GNRs were purified from hexadecyltrimethylammonium bromide (CTAB) and coated with polyethylene glycol (PEG) to obtain GNR-PEG complexes suitable for in vivo applications. Intravenous administration of the purified GNR-PEG complexes to mice resulted in an enhanced contrast of normal tissues and blood vessels as compared to ordinary nude mice. In parallel with optoacoustic imaging we investigated the accumulation of GNRs in liver using invasive analytical techniques. Maximum levels of GNRs in liver macrophages were observed after 48-72 hours post-injection, followed by slow clearance trend after 8 days. Optoacoustic imaging revealed redistribution of GNR in mouse organ and tissues: in the initial hours, accumulation of GNRs is seen predominantly in the periphery of the mouse, while a gradual increase of GNR levels in liver, spleen and kidneys is seen in 1 and 24 hours.
Cell viability studies of PEG-thiol treated gold nanorods as optoacoustic contrast agents
Annals Surg Oncology, 2009
Rod shaped gold nanoparticles are synthesized using cetyltriammonium bromide (CTAB) as a major component of growth solutions. This surfactant is toxic to cells, but is at the moment unavoidable when monodisperse and high yield nanorods are to be synthesized. CTAB is found coating side walls of the nanoparticles and plays a role in maintaining colloidal stability. It may be displaced using thiolated PEG which is non-toxic to cells. Here we report on systematic studies of cell viability of such PEGylated nanorods on an SKBR3 cell-line using the MTS assay. These PEGylated particles are characterized using electron microscopy, optical spectroscopy and zeta potential measurements. It is expected that such treatment will be crucial in making nanorods compatible for in vivo biomedical applications.
Cell viability studies of PEG-thiol treated gold nanorods as optoacoustic contrast agents
Photons Plus Ultrasound: Imaging and Sensing 2009, 2009
Rod shaped gold nanoparticles are synthesized using cetyltriammonium bromide (CTAB) as a major component of growth solutions. This surfactant is toxic to cells, but is at the moment unavoidable when monodisperse and high yield nanorods are to be synthesized. CTAB is found coating side walls of the nanoparticles and plays a role in maintaining colloidal stability. It may be displaced using thiolated PEG which is non-toxic to cells. Here we report on systematic studies of cell viability of such PEGylated nanorods on an SKBR3 cell-line using the MTS assay. These PEGylated particles are characterized using electron microscopy, optical spectroscopy and zeta potential measurements. It is expected that such treatment will be crucial in making nanorods compatible for in vivo biomedical applications.
Photons Plus Ultrasound: Imaging and Sensing 2011, 2011
We used a three-dimensional optical tomogaphy system that was previously developed to create high contrast maps of optical absorbance of mice tissues. In this study, animals were scanned before and after injection of gold nanorods (GNRs) at different time periods. As-synthesized GNRs were purified from hexadecyltrimethylammonium bromide (CTAB) and coated with polyethylene glycol (PEG) to obtain GNR-PEG complexes suitable for in vivo applications. Intravenous administration of the purified GNR-PEG complexes to mice resulted in an enhanced contrast of normal tissues and blood vessels as compared to ordinary nude mice. In parallel with optoacoustic imaging we investigated the accumulation of GNRs in liver using invasive analytical techniques. Maximum levels of GNRs in liver macrophages were observed after 48-72 hours post-injection, followed by slow clearance trend after 8 days. Optoacoustic imaging revealed redistribution of GNR in mouse organ and tissues: in the initial hours, accumulation of GNRs is seen predominantly in the periphery of the mouse, while a gradual increase of GNR levels in liver, spleen and kidneys is seen in 1 and 24 hours.
High Sensitivity of In Vivo Detection of Gold Nanorods Using a Laser Optoacoustic Imaging System
Nano Letters, 2007
The development of a contrast agent for a laser optoacoustic imaging system (LOIS) can significantly widen preclinical and clinical applications of this imaging modality for early detection of cancerous tumors. Gold nanorods were engineered to enhance the contrast for optoacoustic imaging. Under in vivo conditions, 25 µL of gold nanorods solution at a concentration of 1.25 pM were injected into nude mice and detected using a single-channel acoustic transducer. LOIS was used to visualize the distribution of gold nanoparticles at a concentration of 125 pM in vivo when 100 µL of solution of gold nanoparticles was delivered subcutaneously. Our results suggest that LOIS can be used for in vivo detection of gold nanorods at low concentrations and the nanoparticles can be engineered to enhance the diagnostic power of optoacoustic imaging.
Molecular Imaging and Biology, 2004
Optoacoustic tomography (OAT) is a novel medical imaging method that uses optical illumination and ultrasonic detection to produce deep tissue images based on their light absorption. Abnormal angiogenesis in advanced tumors, that increases the blood content of the tumor, is an endogenous contrast agent for OAT. In early stages, however, angiogenesis is not sufficient to differentiate a tumor from normal tissue; justifying the application of an exogenous contrast agent. We have developed a molecular based contrast agent composed of gold nanoparticles conjugated to a monoclonal antibody that improves OAT imaging to potentiate its use in imaging deep tumors in early stages of cancer or metastatic lesions. PROCEDURE: Due to their strong optoacoustic signal, we used gold nanoparticles (NPs) as a contrast agent. To target NPs to breast cancer cells, we conjugated NPs to a monoclonal antibody that specifically binds cell surface receptors known to be overexpressed in human breast tumors.
Gold Nanorods as Contrast Agent for Photoacoustic Imaging (PAI) of Breast Cancer
IOP Conference Series: Materials Science and Engineering, 2020
Gold Nanorods (AuNRs) can play a fundamental role in the enhancement of photoacoustic imaging (PAI). This is due to their high and tunable optical absorption cross-section. Normally, the most convenient and highly stable AuNRs are synthesized using Cetyltrimethylammonium bromide (CTAB) as a surfactant. In this work, surface modification with poly ethylene glycol (PEGylation) and Silica coating (SiO2-coating) were applied to help in reducing toxicity of CTAB capped AuNRs. Breast cancer cell line (MDA-MB-231) was used to assess the modified AuNRs as contrast agents. A much brighter PAI of cells loaded with SiO2-coated AuNRs was obtained. Such an enhanced PA image is due to the larger cellular uptake, as observed from bright field microscope images taken for the cells. On the other hand, the corresponding PA image for cells with PEGylated AuNRs is diminished. The increase in cell uptake, in case of SiO2-coated AuNRs, could result due to the adsorption of protein, contained in the cell ...
Photons Plus Ultrasound: Imaging and Sensing 2012, 2012
Gold nanorods (GNR) with a peak absorption wavelength of 760 nm were prepared using a seed-mediated method. A novel protocol has been developed to replace hexadecyltrimethylammonium bromide (CTAB) on the surface of GNR with 16-mercaptohexadecanoic acid (MHDA) and metoxy-poly(ethylene glycol)-thiol (PEG), and the monoclonal antibodies: HER2 or CD33. The physical chemistry property of the conjugates was monitored through optical and zetapotential measurements to confirm surface chemistry. The plasmon resonance is kept in the near infrared area, and changes from strong positive charge for GNR-CTAB to slightly negative for GNR-PEG-mAb conjugates are observed. The conjugates were investigated for different cells lines: breast cancer cells and human leukemia lines in vivo applications. These results demonstrate successful tumor accumulation of our modified PEG-MHDA conjugates of GNR for HER2/neu in both overexpressed breast tumors in nude mice, and for thermolysis of human leukemia cells in vitro. The conjugates are non-toxic and can be used in pre-clinical applications, as well as molecular and optoacoustic imaging, and quantitative sensing of biological substrates. several research groups 4,6,19-21 . However, the conjugation processes are in need of improvement. Most protocols are hard to adapt to large-scale manufacturing of highly concentrated conjugates with strong affinity toward factors such as biochemical and physiological conditions of the cells and organs of the body 22 . In these studies, we adopted a published methodology of GNR fabrication 7,23,24 to get high yields of narrow band GNR with an optical absorption centered at 760 nm. The manufactured nanorods were pegylated and conjugated with monoclonal antibody (mAb) to become non-toxic in animals as biocompatible OA contrast agents. We characterized the conjugation efficiency of the GNRs mAb by comparing the efficiency of antibody binding of the GNRs before and after pegylation. We demonstrated new order of PEG-coated gold nanorods monoclonal antibody conjugates in preclinical research with optoacoustic tomography, photothermal therapy and sensing