Multifunctional theranostic gold nanoparticles for targeted CT imaging and photothermal therapy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102652/1/cmmi1563.pd

A brief account of nanoparticle contrast agents for photoacoustic imaging

Photoacoustic imaging (PAI) is a hybrid, nonionizing modality offering excellent spatial resolution, deep penetration, and high soft tissue contrast. In PAI, signal is generated based on the absorption of laser-generated optical energy by endogenous tissues or exogenous contrast agents leading to acoustic emissions detected by an ultrasound transducer. Research in this area over the years has shown that PAI has the ability to provide both physiological and molecular imaging, which can be viewed alone or used in a hybrid modality fashion to extend the anatomic and hemodynamic sensitivities of clinical ultrasound. PAI may be performed using inherent contrast afforded by light absorbing molecules such as hemoglobin, myoglobin, and melanin or exogenous small molecule contrast agent such as near infrared dyes and porphyrins. However, this review summarizes the potential of exogenous nanoparticle-based agents for PAI applications including contrast based on gold particles, carbon nanotubes, and encapsulated copper compounds

Cellular trafficking of Sn-2 phosphatidylcholine prodrugs studied with fluorescence lifetime imaging and super-resolution microscopy

While th

Rapid Synthesis of Near Infrared Polymeric Micelles for Real-Time Sentinel Lymph Node Imaging

In this manuscript a synthetic methodology for developing sub 20 nm sized polymeric micellar nanoparticles designed for extravascular imaging and therapy is revealed. A simple, one-pot method is followed, which involves a rapid co-self-assembly of an amphiphilic diblock copolymer (PS-b-PAA) and polyoxyethylene (80) sorbitan monooleate in water. Sorbitan monooleate imparts stability to the micelles and helps to drive down the particle size below 20 nm. The particles are incorporated with a water soluble dye ADS832WS, which absorbs in the near infrared range (λ_(ex) = 832 nm) for sensitive detection with optical and photoacoustic imaging techniques. A candidate lipophilic anti-angiogenic therapeutic agent fumagillin was also incorporated with high entrapment (>95%) efficiency. The effectiveness of this theranostic platform for real-time, high-resolution intraoperative photoacoustic imaging for facilitating direct assessment of the sentinel lymph nodes (SLN) in breast cancer staging is demonstrated. The technique offers huge potential providing faster resection of SLN and may minimize complications caused by axillary exploration due to mismarking with dyes or low-resolution imaging techniques. Finally, the biodistribution and organ accumulation of the intravenously and intradermally injected particles are studied in a rodent model by optical imaging. Data suggest that intraveneously injected NIR-polymeric nanoparticles follow a typical bio-distribution clearance path through the reticuloendothelial (RES) system. For the intradermally injected particles, a slower mechanism of clearance is noticed

A Facile Synthesis of Novel Self-Assembled Gold Nanorods Designed for Near-Infrared Imaging

Molecular imaging techniques now allow recognition of early biochemical, physiological, and anatomical changes before manifestation of gross pathological changes. Photoacoustic imaging represents a novel non-ionizing detection technique that combines the advantages of optical and ultrasound imaging. Noninvasive photoacoustic tomography (PAT) imaging in combination with nanoparticle-based contrast agents show promise in improved detection and diagnosis of cardiovascular and cancer related diseases. In this report, a novel strategy is introduced to achieve self-assembled colloidal gold nanorods, which are constrained to the vasculature. Gold nanorods (2–4 nm) were incorporated into the core of self-assembled lipid-encapsulated nanoparticles (sGNR) (∼130 nm), providing more than hundreds of gold atoms per nanoparticle of 20% colloid suspension. The physico-chemical characterization in solution and anhydrous state with analytical techniques demonstrated that the particles were spherical and highly mono dispersed. In addition to the synthesis and characterization, sensitive near-infrared photoacoustic detection was impressively demonstrated in vitro

Detection and quantification of angiogenesis in experimental valve disease with integrin-targeted nanoparticles and 19-fluorine MRI/MRS

<p>Abstract</p> <p>Background</p> <p>Angiogenesis is a critical early feature of atherosclerotic plaque development and may also feature prominently in the pathogenesis of aortic valve stenosis. It has been shown that MRI can detect and quantify specific molecules of interest expressed in cardiovascular disease and cancer by measuring the unique fluorine signature of appropriately targeted perfluorocarbon (PFC) nanoparticles. In this study, we demonstrated specific binding of α_νβ₃integrin targeted nanoparticles to neovasculature in a rabbit model of aortic valve disease. We also showed that fluorine MRI could be used to detect and quantify the development of neovasculature in the excised aortic valve leaflets.</p> <p>Methods</p> <p>New Zealand White rabbits consumed a cholesterol diet for ~180 days and developed aortic valve thickening, inflammation, and angiogenesis mimicking early human aortic valve disease. Rabbits (n = 7) were treated with α_νβ₃integrin targeted PFC nanoparticles or control untargeted PFC nanoparticles (n = 6). Competitive inhibition <it>in vivo </it>of nanoparticle binding (n = 4) was tested by pretreatment with targeted nonfluorinated nanoparticles followed 2 hours later by targeted PFC nanoparticles. 2 hours after treatment, aortic valves were excised and ¹⁹F MRS was performed at 11.7T. Integrated ¹⁹F spectral peaks were compared using a one-way ANOVA and Hsu's MCB (multiple comparisons with the best) post hoc t test. In 3 additional rabbits treated with α_νβ₃integrin targeted PFC nanoparticles, ¹⁹F spectroscopy was performed on a 3.0T clinical scanner. The presence of angiogenesis was confirmed by immunohistochemistry.</p> <p>Results</p> <p>Valves of rabbits treated with targeted PFC nanoparticles had 220% more fluorine signal than valves of rabbits treated with untargeted PFC nanoparticles (p < 0.001). Pretreatment of rabbits with targeted oil-based nonsignaling nanoparticles reduced the fluorine signal by 42% due to competitive inhibition, to a level not significantly different from control animals. Nanoparticles were successfully detected in all samples scanned at 3.0T. PECAM endothelial staining and α_νβ₃integrin staining revealed the presence of neovasculature within the valve leaflets.</p> <p>Conclusion</p> <p>Integrin-targeted PFC nanoparticles specifically detect early angiogenesis in sclerotic aortic valves of cholesterol fed rabbits. These techniques may be useful for assessing atherosclerotic components of preclinical aortic valve disease in patients and could assist in defining efficacy of medical therapies.</p

Near infrared photoacoustic detection of sentinel lymph nodes with gold nanobeacons

Detection of sentinel lymph node (SLN) using photoacoustic imaging is an emerging technique for noninvasive axillary staging of breast cancer. Due to the absence of intrinsic contrast inside the lymph nodes, exogenous contrast agents are used for photoacoustic detection. In this work, we have demonstrated near infrared detection of SLN with gold nanobeacons (GNBs) providing the photoacoustic contrast in a rodent model. We found that size dictates the in vivo characteristics of these nanoparticles in SLN imaging. Larger nanobeacons with high payloads of gold were not as efficient as smaller size nanobeacons with lower payloads for this purpose. Colloidal GNBs were designed as a nanomedicine platform with “soft” nature that is amenable to bio-elimination, an essential feature for in vivo efficacy and safety. The GNBs were synthesized as lipid- or polymer-encapsulated colloidal particles incorporating tiny gold nanoparticles (2–4 nm) in three tunable sizes (90 nm, 150 nm and 290 nm). Smaller GNBs were noted trafficking through the lymphatic system and accumulating more efficiently in the lymph nodes in comparison to the bigger nanoagents. At 20 min, the GNBs reached the SLN and were no longer observed within the draining lymphatic vessel. Within 1 h post-injection, the contrast ratio of the lymph nodes with the surrounding blood vessels was 9:1. These findings were also supported by analytical measurements of the ex vivo tissue samples. Results indicate that cumulative nanoparticle deposition in lymph nodes is size dependent and that high payloads of gold, although offering greater contrast in vitro, may yield nanoagents with poor intradermal migration and lymphatic transport characteristics