Preclinical evaluation of Raman nanoparticle biodistribution for their potential use in clinical endoscopy imaging.

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.

In vivo behavior of large doses of ultrashort and full-length single-walled carbon nanotubes after oral and intraperitoneal administration to Swiss mice.

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.

Serine-derivatized gadonanotubes as magnetic nanoprobes for intracellular labeling.

Gadonanotubes (GNTs), which are powerful new T(1)-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 x 10(9) Gd(3+) ions/cell) with no observable cytotoxicity. Cell pellets derived from the ser-GNT labeled cells give bright T(1)-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.

Catalytic synthesis of amino acid and peptide derivatized gadonanotubes.

A new Rh(6)(CO)(16)-catalyzed functionalization of gadonanotube MRI probes offers the opportunity to prepare a number of amino acid and peptide derivatized gadonanotubes under RT conditions, containing, for example, the cyclic RGD peptide for the biological targeting of cancer.

Detecting and treating cancer with nanotechnology.

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.

Gadonanotubes as ultrasensitive pH-smart probes for magnetic resonance imaging.

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.

Carbon nanostructures as a new high-performance platform for MR molecular imaging.

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.

Fullerene (C60) immunoconjugates: interaction of water-soluble C60 derivatives with the murine anti-gp240 melanoma antibody.

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