Nanoprobes, Inc.

Other

Assoicated Universties, Inc.

The United States of America As Represented by the Department of Energy

Brookhaven Science Associates, Lcc

James F Hainfeld

Daniel N Slatkin

Richard D Powell

Vishwas N Joshi

Frederic R Furuya

Wenqiu Liu

F Avraham Dilmanian

Robert D Leone

Glenn R Gaudette

Edmund Gutierrez

David J Anchel

Pantaleo Romanelli

Gerard M Morris

Vishwas Joshi

Described herein are iodine-based particles which can be used as contrast agents for x-ray radiology. Also described herein are methods, software modules and hardware modules for imaging iodine-based particles.

Iodine-based particles

Disclosed herein are compositions and methods for increasing the infrared absorptivity of a therapeutic target. Also disclosed are methods for detecting or ablating a therapeutic target that include providing a nanoparticle composition for increasing the infrared absorptivity of the therapeutic target. Subsequently, the therapeutic target having increased infrared absorptivity is exposed to a therapeutically effective dose of infrared irradiation to effect its detection or ablation. In addition, a method is disclosed for treating a subject suffering from a tumor by providing to the tumor a nanoparticle composition for increasing its infrared absorptivity. The tumor having increased infrared absorptivity is then heated by exposing it to a therapeutically effective dose of infrared irradiation.

Gold nanoparticles for selective IR heating

The present invention provides methods of using metal nanoparticles 0.5 to 400 nm in diameter to enhance the dose and effectiveness of x-rays or of other kinds of radiation in therapeutic regimes of ablating a target tissue, such as tumor. The metal nanoparticles can be administered intravenously, intra-arterially, or locally to achieve specific loading in and around the target tissue. The metal nanoparticles can also be linked to chemical and/or biochemical moieties which bind specifically to the target tissue. The enhanced radiation methods can also be applied to ablate unwanted tissues or cells ex vivo.

Methods of enhancing radiation effects with metal nanoparticles

The present invention provides compositions, kits, assemblies of articles and methodology for carrying out processes that permit biological enzymes to act directly on metals and metal particles. In particular, the invention concerns using enzymes to selectively deposit metal to the vicinity of a target molecule. The invention also relates to linking of metals to enzyme substrates, control of enzymatic metal deposition and applications of enzymatic metal deposition to sensitively and selectively detect target molecules such as biomarkers in various biological samples, such as chromogenic immunohistochemical (IHC) detection in situ by using microscopy.

Kit for enzymatic deposition of a metal

Described herein are nanoparticles that are coated with a bilayer of molecules formed from surface binding molecules and amphiphatic molecules. The bilayer coating self assembles on the nanoparticles from readily available materials/molecules. The modular design of the bilayer coated nanoparticles provides a means for readily and efficiently optimizing the properties of the bilayer coated nanoparticle compositions. Also described herein are uses of such nanoparticles in medicine, laboratory techniques, industrial and commercial applications.

Functional associative coatings for nanoparticles

A test agent includes a composite probe having at least one nanoparticle having multiple metal atoms, a directing agent, and an enzyme. The directing agent attaches the probe to a target in a test sample. The test sample and bound probe are then treated with an enzyme substrate. A method of detecting a target in a test sample includes exposing the test sample to the probe, then treating the test sample with an enhancement or development solution to deposit at least one of a fluorophore, a chromogen, or a metal.

Detecting a target using a composite probe comprising a directing agent, a metal nanoparticle and an enzyme

Disclosed embodiments concern site-specific, enzymatic-directed deposition of elemental metal for in-situ analysis. Enzyme substrates are contacted with metal ions and subsequently direct the deposition of elemental metals. Sensitive and selective detection of target molecules, such as biomarkers in various biological samples, can be obtained using various methods, such as in-situ chromogenic immunohistochemical (IHC) detection with bright field light microscopy.

Method for detecting a target using enzyme directed deposition of elemental metal

A method of assisting recovery of an injury site of the central nervous system (CNS) or treating a disease includes providing a therapeutic dose of X-ray radiation to a target volume through an array of parallel microplanar beams. The dose to treat CNS injury temporarily removes regeneration inhibitors from the irradiated site. Substantially unirradiated cells surviving between beams migrate to the in-beam portion and assist recovery. The dose may be staggered in fractions over sessions using angle-variable intersecting microbeam arrays (AVIMA). Additional doses are administered by varying the orientation of the beams. The method is enhanced by injecting stem cells into the injury site. One array or the AVIMA method is applied to ablate selected cells in a target volume associated with disease for palliative or curative effect. Atrial fibrillation is treated by irradiating the atrial wall to destroy myocardial cells while continuously rotating the subject.

Methods for assisting recovery of damaged brain and spinal cord and treating various diseases using arrays of x-ray microplanar beams

The present invention provides methods for the use of enzymes to selectively deposit metal to the vicinity of a target molecule. The invention also relates to applications of enzymatic metal deposition to sensitively and selectively detect target molecules such as biomarkers in various biological samples, such as chromogenic immunohistochemical (IHC) detection in situ by using bright field light microscope.

Method for detecting a target molecule by metal deposition

Disclosed are methods and materials for utilizing enzymes to act on metal ions in solution so that the ions are reduced to metal. Additionally disclosed is how to use enzymes to accumulate metal particles. The alteration of metal particles by enzymes interacting with the organic shell of the particles is also described. These methods enable a wide range of applications including sensitive detection of genes and proteins, use as probes for microscopy, nanofabrication, biosensors, and remediation.

Method of reducing metal ions to elemental metal in the vicinity of an oxido-reductase enzyme

The present invention provides methods of using metal nanoparticles 0.5 to 400 nm in diameter to enhance the dose and effectiveness of x-rays or of other kinds of radiation in therapeutic regimes of ablating a target tissue such as tumor. The metal nanoparticles can be administered intravenously, intra-arterially, or locally to achieve specific loading in and around the target tissue. The metal nanoparticles can also be linked to chemical and/or biochemical moieties which bind specifically to the target tissue. The enhanced radiation methods can also be applied to ablate unwanted tissues or cells ex vivo.

Disclosed are methods and materials for utilizing enzymes to act on metal ions in solution so that the ions are reduced to metal and deposited. These methods enable a wide range of applications including the detection of one or more constituents in a test sample.

Test methods using enzymatic deposition and alteration of metals

A method of performing radiation therapy includes delivering a therapeutic dose such as X-ray only to a target (e.g., tumor) with continuous broad beam (or in-effect continuous) using arrays of parallel planes of radiation (microbeams/microplanar beams). Microbeams spare normal tissues, and when interlaced at a tumor, form a broad-beam for tumor ablation. Bidirectional interlaced microbeam radiation therapy (BIMRT) uses two orthogonal arrays with inter-beam spacing equal to beam thickness. Multidirectional interlaced MRT (MIMRT) includes irradiations of arrays from several angles, which interleave at the target. Contrast agents, such as tungsten and gold, are administered to preferentially increase the target dose relative to the dose in normal tissue. Lighter elements, such as iodine and gadolinium, are used as scattering agents in conjunction with non-interleaving geometries of array(s) (e.g., unidirectional or cross-fired (intersecting) to generate a broad beam effect only within the target by preferentially increasing the valley dose within the tumor.

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Shoreham, NY, United States of America

James F Hainfeld