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Raman imaging offers unsurpassed sensitivity and multiplexing capabilities. However, its limited depth of light penetration makes direct clinical translation challenging. Therefore, a more suitable way to harness its attributes in a clinical setting would be to couple Raman spectroscopy with endoscopy. The use of an accessory Raman endoscope in conjunction with topically administered tumor-targeting Raman nanoparticles during a routine colonoscopy could offer a new way to sensitively detect dysplastic lesions while circumventing Raman's limited depth of penetration and avoiding systemic toxicity. In this study, the natural biodistribution of gold surface-enhanced Raman scattering (SERS) nanoparticles is evaluated by radiolabeling them with (64) Cu and imaging their localization over time using micropositron emission tomography (PET). Mice are injected either intravenously (IV) or intrarectally (IR) with approximately 100 microcuries (μCi) (3.7 megabecquerel (MBq)) of (64) Cu-SERS nanoparticles and imaged with microPET at various time points post injection. Quantitative biodistribution data are obtained as % injected dose per gram (%ID g(-1)) from each organ, and the results correlate well with the corresponding microPET images, revealing that IV-injected mice have significantly higher uptake (p < 0.05) in the liver (5 h = 8.96% ID g(-1); 24 h = 8.27% ID g(-1)) than IR-injected mice (5 h = 0.09% ID g(-1); 24 h = 0.08% ID g(-1)). IR-injected mice show localized uptake in the large intestine (5 h = 10.37% ID g(-1); 24 h = 0.42% ID g(-1)) with minimal uptake in other organs. Raman imaging of excised tissues correlate well with biodistribution data. These results suggest that the topical application of SERS nanoparticles in the mouse colon appears to minimize their systemic distribution, thus avoiding potential toxicity and supporting the clinical translation of Raman spectroscopy as an endoscopic imaging tool.

Photoacoustic tomography is a rapidly growing imaging modality that can provide images of high spatial resolution and high contrast at depths up to 5 cm. We report here the design, synthesis, and evaluation of an activatable probe that shows great promise for enabling detection of the cleaved probe in the presence of high levels of nonactivated, uncleaved probe, a difficult task to attain in absorbance-based modality. Before the cleavage by its target, proteolytic enzyme MMP-2, the probe, an activatable cell-penetrating peptide, Ceeee[Ahx]PLGLAGrrrrrK, labeled with two chromophores, BHQ3 and Alexa750, shows photoacoustic signals of similar intensity at the two wavelengths corresponding to the absorption maxima of the chromophores, 675 and 750 nm. Subtraction of the images taken at these two wavelengths makes the probe effectively photoacoustically silent, as the signals at these two wavelengths essentially cancel out. After the cleavage, the dye associated with the cell-penetrating part of the probe, BHQ3, accumulates in the cells, while the other dye diffuses away, resulting in photoacoustic signal seen at only one of the wavelengths, 675 nm. Subtraction of the photoacoustic images at two wavelengths reveals the location of the cleaved (activated) probe. In the search for the chromophores that are best suited for photoacoustic imaging, we have investigated the photoacoustic signals of five chromophores absorbing in the near-infrared region. We have found that the photoacoustic signal did not correlate with the absorbance and fluorescence of the molecules, as the highest photoacoustic signal arose from the least absorbing quenchers, BHQ3 and QXL 680.

Coordination complexes containing extended metal–oxygen frameworks have been studied for a number of applications, including catalysis and as optical materials; however, very few neutral complexes that contain extended metal–oxygen frameworks have been characterized. The new hexanuclear, mixed-valence MoV/MoVI coordination complex Mo6O13(Hsal)2(sal)2(acac)2 has been synthesized by direct reaction of salicylic acid (2-HOC6H4CO2H; H2sal) with Mo(O)2(acac)2. The mixed-valence compound is composed of two edge-sharing Mo4(μ-O)4 rings, in which four Mo atoms are MoVI and two are MoV. The tetranuclear complex Mo4O10(acac)4 was obtained from residual washings of the same reaction and is composed of a single Mo4(μ-O)4 ring having only MoVI atoms. XPS studies confirmed that the hexanuclear complex contains both MoV and MoVI. Magnetic measurements reveal that the hexanuclear complex is diamagnetic suggesting an electron–electron coupling between the two MoV centers through an oxo-bridge.

New nanoparticle shapes of iron oxide (FexOFe3O4, where 0.8

A new procedure to purify HiPco single-walled carbon nanotubes (SWCNTs) from iron catalyst impurity is introduced. The protocol, which uses liquid bromine at room temperature (RT) as an oxidant, improves nanotube purity from iron by a factor of approximately 10, while maintaining good nanotube integrity as demonstrated by near infrared (NIR) luminescence and absorbance measurements. When HiPco SWCNTs are dissolved in RT Br2(l) (free of O2 and H2O), the metallic iron impurity is quickly oxidized to its bromide salt and easily removed by aqueous washing or by washing with dilute acid. The iron content (by ICP-AE) for the purified SWCNT material was 2.8–3.6% by weight (for three different samples) for a single purification step, but could be lowered to 1.6–1.8% with an additional purification cycle. Characterization of the resulting purified SWCNT material has been achieved by TEM imaging, XPS, ICP-AE analysis, Raman spectroscopy, electronic absorption spectroscopy, and by NIR photoluminescence measurements. Finally, the new Br2(l) purification procedure has been compared to and contrasted with other established purification procedures for HiPco SWCNTs and found to be a highly desirable alternative.

We report the functionalization of individual ultra-short (20–80 nm lengths) single-walled carbon nanotubes (US-tubes) via in situ Bingel cyclopropanation. Upon chemical reduction (K°/THF) of bundled US-tubes, the bundling forces are electrostatically overcome to yield single, negatively charged US-tubes in solution. These single US-tubes can then be functionalized with malonic acid bis-(3-tert-butoxycarbonylaminopropyl) ester using Bingel chemistry (CBr4/DBU) to yield 4–5 adducts nm−1, as determined by x-ray photoelectron spectroscopy (XPS). The derivatized US-tubes remain as individuals after functionalization and charge quenching. Thermogravimetric analysis (TGA) and solid-state NMR spectroscopy confirmed covalent attachment of the adducts and indicated tight wrapping of the adduct arms about the US-tubes. The resulting debundled and derivatized US-tubes serve as a prototype single-molecule-like 'capsule' for the containment and delivery of medically-useful payloads.

Carbon nanotube (CNT) materials are of special interest as potential tools for biomedical applications. However, available toxicological data concerning single-walled carbon nanotubes (SWNTs) and multiwalled carbon nanotubes (MWNTs) remain contradictory. Here, we compared the effects of SWNTs as a function of dose, length, and surface chemistry in Swiss mice. Transmission electron microscopy (TEM), Raman, near-infrared (NIR), and X-ray photoelectron spectroscopies have been used to characterize the tested materials. The dose of SWNT materials used in this study is considerably higher than that proposed for most biomedical applications, but it was deemed necessary to administer such large doses to accurately assess the toxicological impact of the materials. In an acute toxicity test, SWNTs were administered orally at a dose level of 1000 mg/kg bodyweight (b.w.). Neither death nor growth or behavioral troubles were observed. After intraperitoneal administration, SWNTs, irrespective of their length or dose (50-1000 mg/kg b.w.), can coalesce inside the body to form fiberlike structures. When structure lengths exceeded 10 mum, they irremediably induced granuloma formation. Smaller aggregates did not induce granuloma formation, but they persisted inside cells for up to 5 months after administration. Short (300 nm) well-individualized SWNTs can escape the reticuloendothelial system to be excreted through the kidneys and bile ducts. These findings suggest that if the potential of SWNTs for medical applications is to be realized, they should be engineered into discrete, individual "molecule-like" species.

Gadonanotubes (GNTs), which are powerful new T1-weighted MRI contrast agents, were derivatized with serine amino acid substituents to produce water-soluble (2 mg ml−1) ser-gadonanotubes (ser-GNs) as magnetic nanoprobes for intracellular labeling. The ser-GNTs were used to efficiently label MCF-7 human breast cancer cells (1.5 × 109 Gd3+ ions/cell) with no observable cytotoxicity. Cell pellets derived from the ser-GNT labeled cells give bright T1-weighted MR images, confirming that the ser-GNTs are a promising new nanoprobe technology for magnetic cell labeling and possibly for in vivo cellular trafficking. Copyright © 2010 John Wiley & Sons, Ltd.

Nanotechnology offers many opportunities for enhanced diagnostic and therapeutic medicine against cancer and other diseases. In this review, the special properties that result from the nanoscale size of quantum dots, metal colloids, superparamagnetic iron oxide, and carbon-based nanostructures are reviewed and interpreted against a background of the structural and electronic detail that gives rise to their nanotechnologic behavior. The detection and treatment of cancer is emphasized, with special attention paid to the biologic targeting of the disease. The future of nanotechnology in cancer research and clinical practice is projected to focus on ‘theranostic’ nanoparticles that are both diagnostic and therapeutic by design.

Over the last several years, great interest has developed in the potential use of carbon nanostructures (C60 fullerenes and nanotubes) in medicine. In some cases, medical agents derived from these materials have demonstrated greater efficacy than existing clinical agents in many imaging and therapeutic applications. This chapter provides an overall review of the application of these materials in the area of magnetic resonance imaging (MRI), with an emphasis on their future applications in targeted MR molecular imaging for the early detection of cancer and other life-threatening diseases.

Over the last several years, great interest has developed in the potential use of carbon nanostructures (C60 fullerenes and nanotubes) in medicine. In some cases, medical agents derived from these materials have demonstrated greater efficacy than existing clinical agents in many imaging and therapeutic applications. This chapter provides an overall review of the application of these materials in the area of magnetic resonance imaging (MRI), with an emphasis on their future applications in targeted MR molecular imaging for the early detection of cancer and other life-threatening diseases.

The first fullerene (C60) immunoconjugates have been prepared and characterized as an initial step toward the development of fullerene immunotherapy (FIT).

X-ray photoelectron spectroscopy (XPS) along with inductively coupled plasma analysis (ICP-AE) and Raman spectroscopy have been used to define the location and to quantify the amount of iodine in HiPco SWNT samples loaded with molecular I(2) via sublimation (I(2)-SWNTs). The exterior-adsorbed I(2) can be removed (as I(-)) by reducing the sample of filled nanotubes with Na(0)/THF or by heating the I(2)-SWNTs to 300 degrees C (without reduction), leaving I(2) contained only within the interior of the SWNTs (I(2)@SWNTs) as proven by XPS. These I(2)@SWNTs contain approximately 25 wt % of I(2) and are stable without the loss of I(2) even after exposure to additional reduction with Na(0)/THF or upon heating to ca. 500 degrees C.

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With their nanoscalar, superparamagnetic Gd(3+)-ion clusters (1 x 5 nm) confined within ultrashort (20-80 nm) single-walled carbon nanotube capsules, gadonanotubes are high-performance T1-weighted contrast agents for magnetic resonance imaging (MRI). At 1.5 T, 37 degrees C, and pH 6.5, the r1 relaxivity (ca. 180 mM(-1) s(-1) per Gd(3+) ion) of gadonanotubes is 40 times greater than any current Gd(3+) ion-based clinical agent. Herein, we report that gadonanotubes are also ultrasensitive pH-smart probes with their r1/pH response from pH 7.0-7.4 being an order of magnitude greater than for any other MR contrast agent. This result suggests that gadonanotubes might be excellent candidates for the development of clinical agents for the early detection of cancer where the extracellular pH of tumors can drop to pH=7 or below. In the present study, gadonanotubes have also been shown to maintain their integrity when challenged ex vivo by phosphate-buffered saline solution, serum, heat, and pH cycling.