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Contents: News Stories, 2002


September 9, 2002

Nanoprobes Receives Phase I SBIR Grant to Research Novel MRI Contrast Agents

The National Cancer Institute (National Institutes of Health) has recently awarded a Phase I SBIR grant to Nanoprobes, Incorporated (Yaphank, NY) for one year, effective August 1, to develop a new type of contrast agents for magnetic resonance imaging (MRI) based on metal nanoparticles, both free and conjugated to targeting agents such as antibodies and proteins.

In preliminary MRI studies in animals, the new reagents gave excellent definition of some types of brain tumors that were undetectable using the commonly used reagent, gadodiamide. Furthermore, initial toxicity studies indicated very low toxicity levels. The new reagents are chemically cross-linkable to antibodies, proteins, or other targeting agents; this allows targeting to specific regions of interest, such as organs or tumors. One new agent, coupled to antibodies, showed high delivery to antigen in bench tests, indicating a potential for targeted contrast agents for MRI.

The new reagents have many potential applications in both their targeted and non-targeted forms. We plan to develop agents for improved imaging of prostate tumors, brain tumors, angiogenesis, and wounds. This technology will provide both improved sensitivity and specificity for imaging, and also the opportunity - because the new reagents can be synthetically modified to incorporate appropriate chemical properties - to tailor their chemical properties for desired residence times in specific organs or systems of the body for applications such as the imaging of specific organs, or surgical sites during operations.

The metal nanoparticles and conjugates will be synthesized and developed at Nanoprobes. Testing and animial studies will be conducted in collaboration with the Departments of Pharmacology and Diagnostic Imaging and Therapeutics at the University of Connecticut Health Center (Farmington, CT).

Nanoprobes, Inc., founded in November 1990, researches and develops the biomedical and high-technology applications of metal nanoparticles. The company is a leader in immunogold technology, with products which include the 1.4 nm Nanogold® cluster immunoprobes and labeling reagents and the combined fluorescent and gold immunoprobe FluoroNanogold which is used for correlative fluorescence and electron microscopy, and ultrasensitive in situ hybridization detection reagents.

For more information, contact:

James F. Hainfeld, Ph. D.
President
Nanoprobes, Incorporated
95 Horse Block Road
Yaphank, NY 11980-2301

Telephone: (631) 205-9490
Fax: (631) 205-9493
E-mail [email protected]
WWW: www.nanoprobes.com

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September 4, 2002

Nanoprobes wins Phase II STTR Grant to develop Chromogenic In Situ Hybridization Detection Assay

Nanoprobes, Incorporated has received a Phase II Small Business Technology Transfer (STTR) grant of $ 878,529 for two years from the National Cancer Institute (National Institutes of Health) to continue the development of a chromogenic in situ hybridization assay to detect amplification of the Her-2/neu gene. The assay will be used by pathologists and physicians to identify candidates for humanized monoclonal antibody (Herceptin) therapy.

The assay utilizes the small gold particle Nanogold® combined with autometallography, or selective chemical deposition of silver or gold, to generate a dense, black signal which is observed by conventional brightfield microscopy without the need for oil immersion. Staining is permanent, easily seen in a standard light microscope, and readily distinguished from commonly used stains; it does not fade, and is not hampered by autofluorescence. Its high spatial resolution also permits subsequent electron microscopy analysis. During Phase I work, the method was successfully used in a series of 100 specimens, and high concordance was found in an interobserver reproducibility study. The assay was specifically designed for qualitative interpretation, thus simplifying the diagnostic process, and its features make it more convenient than FISH for practicing pathologists. Although initially targeted to Her-2/neu gene amplification, the general method will be applicable to many other conditions. Unlike fluorescence in situ hybridization (FISH), the new method will not require fluorescent optics, and therefore will be more convenient for many practicing pathologists. In the Phase II work, the procedure will be adapted for use on automated platforms, and clinical studies required for regulatory approval will be completed.

Reagents for the new method will be developed at Nanoprobes, Incorporated, and the in situ hybridization assay will be developed and tested at the Cleveland Clinic Foundation by Dr. Raymond R. Tubbs. Clinical studies will also be conducted at the University of Virginia Health Sciences Center in collaboration with Dr. Mark H. Stoler, and the regulatory submissions process will be managed by Lumina Verita (Tucson, AZ); the grant also includes a subcontract to the State University of New York at Stony Brook.

Nanoprobes, Inc., founded in November 1990, researches and develops the biomedical, chemical and high-technology applications of metal nanoparticles and autometallography. The company is a leader in immunogold technology, with products which include the 1.4 nm Nanogold® cluster immunoprobes and labeling reagents, and autometallographic enhancers which are used in light and electron microscopy, biomedical and nanotechnology research.

For more information, contact:

Richard D. Powell, Ph. D.
Research Director
Nanoprobes, Incorporated
95 Horse Block Road
Yaphank, NY 11980-2301

Telephone: (919) 845-6324
Fax: (631) 980-3608
E-mail [email protected]
WWW: www.nanoprobes.com

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July 8, 2002

Nanoprobes Receives Phase II SBIR Grant on Gold Quenched Molecular Beacons

The National Institute of General Medical Sciences (National Institutes of Health) has recently awarded a Phase I SBIR grant to Nanoprobes, Incorporated (Yaphank, NY) of $ 986,617 for two years, effective July 1, to further develop the application of its gold labels as quenchers for fluorescently labeled molecular beacons.

Nanogold®, a 1.4 nm metal cluster compound, is covalently linked to biologically active molecules for use as a structural probe in microscopy, where it is widely used for labeling cellular and tissue components for electron microscope observation. It has also been found to quench fluorescence over short distances, making it ideal for application to molecular beacons. In preliminary experiments published in Nature Biotechnology, Nanogold® has already demonstrated a quenching ability (signal-to-noise ratio) which is greater by up to an order of magnitude than that found with commonly used fluorescent quenchers. The grant will support the synthesis and evaluation of a number of improved gold cluster compounds and nanoparticles which will provide even higher signal-to-noise ratios; furthermore, because gold cluster labels absorb across a large part of the visible spectrum, the same particle formulation can be used in a range of different beacons, potentially simplifying and streamlining beacon manufacture.

This technology will simplify and enhance the real-time detection of specific DNA sequences in cells and other highly localized systems. Because molecular beacons only fluoresce after binding to their target, the specific signal is not affected by the presence of unbound beacon, and therefore unbound beacons need not be removed before observation. This technology may help enable applications such as real-time PCR-based cancer screening, fiber optic biosensors for quickly screening tissues during transplantation and other medical procedures, and portable fetal testing.

Gold cluster labels will be developed and optimized at Nanoprobes, Incorporated by Dr. Richard Powell, Dr. Vishwas Joshi, Dr. Wenqiu Liu, and Theresa Focella, with advice from Dr. James F. Hainfeld. Molecular beacons will be constructed and evaluated at The Rockefeller University, Department of Physics, by Prof. Albert Libchaber and Dr. Benoit Dubertret. In addition, the applications to real-time diagnostics will be investigated in collaboration with Dr. Gary Procop of the Cleveland Clinic Foundation; the grant also includes a subcontract to the Chemical Synthesis Center at the State University of New York at Stony Brook. Research will elucidate the mechanisms by which energy is transferred between fluorescent groups and a variety of metal cluster compounds and nanoparticles. This will enable the selection of particles optimized for highest signal-to-noise and best quenching performance in beacons.

Nanoprobes, Inc., founded in November 1990, researches and develops the biomedical and high-technology applications of metal nanoparticles and autometallography. The company is a leader in immunogold technology, with products which include the 1.4 nm Nanogold® cluster immunoprobes and labeling reagents, the combined fluorescent and gold immunoprobe FluoroNanogold which is used for correlative fluorescence and electron microscopy, and ultrasensitive in situ hybridization detection reagents.

For more information, contact:

Richard D. Powell, Ph. D.
Research Director
Nanoprobes, Incorporated
95 Horse Block Road
Yaphank, NY 11980-2301

Telephone: (919) 845-6324
Fax: (631) 980-3608
E-mail [email protected]
WWW: www.nanoprobes.com

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