Bioconjugated gold nanoparticles as a molecular based contrast agent: implications for imaging of deep tumors using optoacoustic tomography (original) (raw)
Related papers
Progress in Biomedical Optics and Imaging - Proceedings of SPIE, 2006
Advanced optical technologies for in vivo imaging e.g. OCT and confocal reflectance endomicroscopy while being able to image stromal morphology, are unable to image biomolecular changes associated with carcinogenesis. Furthermore, the contrast between neoplastic and normal tissues from such advanced optical technologies is often too low to be of any clinical value. Due to their favorable optical properties including their ability to resonantly scatter light at surface plasmon resonance to present potentially good contrast for reflectance-mode imaging, we aim to develop gold nanoparticles as optical contrast agents coupled with these optical imaging systems to perform cancer targeting bioimaging for early diagnosis of epithelial carcinoma. In this study, 20 nm gold nanoparticles were synthesized and conjugated with anti-EGFR (Epidermal Growth Factor Receptor). EGFR is a cell surface receptor biomarker that is highly expressed in majority of epithelial cancer compared to normal cells. The resulting anti-EGFR conjugated gold nanoparticles were allowed to interact with the nasopharyngeal carcinoma CNE2 cells in vitro. The exact localization of the gold bioconjugates on the cell surface EGFR receptors was investigated using confocal immunofluorescence microscopy. We have demonstrated that the binding and localization of the gold bioconjugates on the cell surface increased the reflectance and scattering properties of the CNE2 cells and provide good optical contrast for the cancer cells under confocal reflectance microscopy. Thus our study has demonstrated the potential of gold nanoparticles to target and illuminate cancer cells for bioimaging.
British Journal of Radiology, 2011
Objectives: Gold nanoparticles are of interest as potential in vivo diagnostic and therapeutic agents, as X-ray contrast agents, drug delivery vehicles and radiation enhancers. The aim of this study was to quantitatively determine their targeting and microlocalisation in mouse tumour models after intravenous injection by using micro-CT. Methods: Gold nanoparticles (15 nm) were coated with polyethylene glycol and covalently coupled to anti-Her2 antibodies (Herceptin). In vitro, conjugates incubated with Her2+ (BT-474) and Her2-(MCF7) human breast cancer cells showed specific targeted binding with a Her2+ to Her2-gold ratio of 39.4¡2.7:1. Nude mice, simultaneously bearing subcutaneous Her2+ and Her2-human breast tumours in opposite thighs were prepared. Gold nanoparticles alone, conjugated to Herceptin or to a non-specific antibody were compared. After intravenous injection of the gold nanoparticles, gold concentrations were determined by atomic absorption spectroscopy. Microlocalisation of gold was carried out by calibrated micro-CT, giving both the radiodensities and gold concentrations in tumour and non-tumour tissue. Results: All gold nanoparticle constructs showed accumulation, predominantly at tumour peripheries. However, the Herceptin-gold nanoparticles showed the best specific uptake in their periphery (15.8¡1.7% injected dose per gram), 1.6-fold higher than Her2-tumours and 22-fold higher than surrounding muscle. Imaging readily enabled detection of small, 1.5 mm-thick tumours. Conclusion: In this pre-clinical study, antibody-targeted 15 nm gold nanoparticles showed preferential uptake in cognate tumours, but even untargeted gold nanoparticles enhanced the visibility of tumour peripheries and enabled detection of millimetre-sized tumours. Micro-CT enabled quantification within various regions of a tumour.
Nanobiotechnology, 2008
Biomedical nanotechnology offers superior potential for diagnostic imaging of malignancy at the microscopic level. In addition to current research focused on dual-imaging and therapeutic applications in vivo, these novel particles may also prove useful for obtaining immediate diagnostic results in vitro at the patient bedside. However, translating the use of nanoparticles for cancer detection to point-of-care applications requires that conditions be optimized such that minimal time is needed for diagnostic results to become available. Thus far, no reports have been published on minimizing the time needed to achieve acceptable optical contrast of cancer cells incubated with nanoparticles. In this study, we demonstrate the use of gold nanoshells targeted to anti-HER2 antibodies that produce sufficient optical contrast with HER2-overexpressing SK-BR-3 breast cancer cells in only 5 min. This work validates the proof of concept that nanoshells targeted to extracellular biomarkers can be used to enhance cancer diagnostic imaging for use in point-of-care applications.
Targeted Gold Nanoparticles Enable Molecular CT Imaging of Cancer
Nano Letters, 2008
X-ray based computed tomography (CT), is among the most convenient imaging/diagnostic tools in hospitals today in terms of availability, efficiency and cost. However, in contrast to magnetic resonance imaging (MRI) and various nuclear medicine imaging modalities, CT is not considered a molecular imaging modality since targeted and molecularly specific contrast agents have not yet been developed. Here we describe a targeted molecular imaging platform that enables, for the first time, cancer detection at the cellular and molecular level with standard clinical CT. The method is based on gold nano-probes that selectively and sensitively target tumor selective antigens, while inducing distinct contrast in CT imaging (increased x-ray attenuation). We present an in vitro proof of principle demonstration for head and neck cancer, showing that the attenuation coefficient for the molecularly targeted cells is over 5 times higher than for identical but untargeted cancer cells or for normal cells. We expect this novel imaging tool to lead to significant improvements in cancer therapy, due to earlier detection, accurate staging and micro-tumor identification.
Stimuli-Responsive Gold Nanoparticles for Cancer Diagnosis and Therapy
Journal of Functional Biomaterials, 2016
An emerging concept is that cancers strongly depend on both internal and external signals for growth and invasion. In this review, we will discuss pathological and physical changes in the tumor microenvironment and how these changes can be exploited to design gold nanoparticles for cancer diagnosis and therapy. These intrinsic changes include extracellular and intracellular pH, extracellular matrix enzymes, and glutathione concentration. External stimuli include the application of laser, ultrasound and X-ray. The biology behind these changes and the chemistry behind the responding mechanisms to these changes are reviewed. Examples of recent in vitro and in vivo studies are also presented, and the clinical implications of these findings are discussed.
Contrast Media & Molecular Imaging, 2015
The utility of nanobodies and conventional antibodies for in vivo imaging is well known, but optimum dosing and timing schedules for one versus the other have not been established. We aimed to improve specific tumor imaging in vivo with nanobodies and conventional antibodies using near-infrared fluorescence (NIRF) imaging. We used ARTC2 expressed on lymphoma cells as a model target antigen. ARTC2-specific nanobody s+16a and conventional antibody Nika102 were labeled with NIRF-dye AF680. In vivo NIRF-imaging of ARTC2-positive and ARTC2-negative xenografts was performed over 24 h post-injection of 5, 10, 25, or 50 μg of each conjugate. Specific target-binding and tissue-penetration were verified by NIRF imaging ex vivo, flow cytometry and fluorescence microscopy. NIRFimaging of s+16a 680 in vivo revealed a six times faster tumor accumulation than of Nika102 680. Using 50 μg of s+16a 680 increased the specific signals of ARTC2-positive tumors without increasing background signals, allowing a tumor-to-background (T/B) ratio of 12.4 ± 4.2 within 6 h post-injection. Fifty micrograms of Nika102 680 increased specific signals of ARTC2-positive tumors but also of ARTC2-negative tumors and background, thereby limiting the T/B ratio to 6.1 ± 2.0. Ten micrograms of Nika102 680 only slightly reduced specific tumor signals but dramatically reduced background signals. Ex vivo analyses confirmed a faster and deeper tumor penetration with s+16a 680. Using nanobody s+16a allowed same-day imaging with a high T/B ratio, whereas antibody Nika102 gave optimal imaging results only 24 h post injection. Nanobody s+16a required a high dose, whereas antibody Nika102 had the best T/Bratio at a low dose. Therefore, timing and dosage should be addressed when comparing nanobodies and conventional antibodies for molecular imaging purposes.
Molecular imaging of carcinogenesis with immuno-targeted nanoparticles
The 26th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 2004
Molecular characterization of cancer could have important clinical benefits such as earlier cancer detection based on molecular characterization, the ability to predict the risk of cancer progression, real time margin detection, the ability to rationally select molecular therapy and to monitor response to the therapy. We present a new class of molecular specific contrast agents for optical imaging of carcinogenesis in vivo -gold nanoparticles conjugated with monoclonal antibodies specific for cancer biomarkers.
In Vivo Detection of Gold Nanoshells in Tumors Using Diffuse Optical Spectroscopy
IEEE Journal of Selected Topics in Quantum Electronics, 2007
This study demonstrates the use of diffuse optical spectroscopy (DOS) for the noninvasive measurement of gold nanoshell concentrations in tumors of live mice. We measured the diffuse optical spectra (500-800 nm) using an optical fiber probe placed in contact with the tissue surface. We performed in vitro studies on tissue phantoms illustrating an accurate measurement of gold-silica nanoshell concentration within 12.6% of the known concentration. In vivo studies were performed on a mouse xenograft tumor model. DOS spectra were measured at preinjection, immediately postinjection, 1 and 24 h postinjection times, and the nanoshell concentrations were verified using neutron activation analysis. Index Terms-Contrast agents, diffuse optical spectroscopy (DOS), diffusion theory, gold nanoparticles, optical imaging. I. INTRODUCTION G OLD nanoshells have recently been demonstrated for use in a new type of laser-induced thermal therapy of tumors [1], [2] and cancerous cell lines [3]. Gold nanoshells are biologically inert and optically tunable nanoparticles composed of silica cores coated with an ultrathin gold layer [4]. The optical properties can be tuned by varying the relative size of the core and the thickness of the shell. In particular, these particles can be designed to absorb near-infrared light, and when irradiated by a laser, provide an exogenous vehicle to convert optical energy into heat. In addition, the particles passively extravasate through the leaky and aberrant blood vessels within tumors, a process known as the enhanced permeability and retention (EPR) effect [5]. Thus, intravenous administration of gold nanoshells leads to nanoparticle accumulation within the Manuscript
Application of gold nanoparticles for early detection of breast cancer cells
Gold nanoparticles (GNPs) have been synthesized by a chemical reduction method using sodium borohydride and functionalized with amino groups on their surface. The GNPs were then conjugated with the anti-HER2 human antibody (trastuzumab) for detecting breast cancer cells. The specific binding of trastuzumab-conjugated GNPs onto the breast cancer cells (KPL4 line) were observed by bright-field and dark-field microscopy and were for the first time observed by scanning electron microscopy and energy dispersive X-ray scanning.