University of Missouri

Cornell University

Memorial Sloan Kettering Cancer Center

Other

Thomas P Quinn

Ulrich B Wiesner

Michelle S Bradbury

Silvia S Jurisson

Michael F Giblin

Jason S Lewis

Kai Ma

Barney Yoo

Natalia G Karasseva

Steven M Larson

Andrew A Burns

Howard Scher

Oula Penate Medina

Feng Chen

Wolfgang Weber

Karim Touijer

Described herein are novel conjugates containing an inhibitor (e.g., a PSMA inhibitor, e.g., a gastrin-releasing peptide receptor inhibitor) and metal chelator that are covalently attached to a macromolecule (e.g., a nanoparticle, a polymer, a protein). Such conjugates exhibit distinct properties over the free, unbound inhibitor/chelator construct.

Inhibitor-functionalized ultrasmall nanoparticles and methods thereof

Disclosed herein are nanoparticle immunoconjugates useful for therapeutics and/or diagnostics. The immunoconjugates have diameter (e.g., average diameter) no greater than 20 nanometers (e.g., as measured by dynamic light scattering (DLS) in aqueous solution, e.g., saline solution). In certain embodiments, the conjugates are silica-based nanoparticles with single chain antibody fragments attached thereto.

Nanoparticle immunoconjugates

The present invention provides a fluorescent silica-based nanoparticle that allows for precise detection, characterization, monitoring and treatment of a disease such as cancer. The nanoparticle has a range of diameters including between about 0.1 nm and about 100 nm, between about 0.5 nm and about 50 nm, between about 1 nm and about 25 nm, between about 1 nm and about 15 nm, or between about 1 nm and about 8 nm. The nanoparticle has a fluorescent compound positioned within the nanoparticle, and has greater brightness and fluorescent quantum yield than the free fluorescent compound. The nanoparticle also exhibits high biostability and biocompatibility. To facilitate efficient urinary excretion of the nanoparticle, it may be coated with an organic polymer, such as poly(ethylene glycol) (PEG). The small size of the nanoparticle, the silica base and the organic polymer coating minimizes the toxicity of the nanoparticle when administered in vivo. In order to target a specific cell type, the nanoparticle may further be conjugated to a ligand, which is capable of binding to a cellular component associated with the specific cell type, such as a tumor marker. In one embodiment, a therapeutic agent may be attached to the nanoparticle. To permit the nanoparticle to be detectable by not only optical fluorescence imaging, but also other imaging techniques, such as positron emission tomography (PET), single photon emission computed tomography (SPECT), computerized tomography (CT), bioluminescence imaging, and magnetic resonance imaging (MRI), radionuclides/radiometals or paramagnetic ions may be conjugated to the nanoparticle.

Multimodal silica-based nanoparticles

The ErbB-2 receptor, a member of the tyrosine kinase type 1 family of receptors, has been implicated in many human malignancies. Bacteriophage display technology was employed to identify peptides that bound to the extracellular domain of human ErbB-2. The peptide KCCYSL, most frequently occurring in the affinity selected population, was chemically synthesized and characterized for its binding activities to the recombinant extracellular domain of ErbB-2. The synthetic peptide exhibits high specificity to ErbB-2 as well as to ErbB-1, another member of ErbB family. Thus, this peptide can be employed in cancer imaging or therapeutic agent targeting to malignant cells ErbB-2 receptor.

ErbB-2 receptor targeting peptide

Erb-2 receptor targeting peptide

A compound for use as a diagnostic or therapeutic pharmaceutical and method of using the same where the compound consists essentially of an alpha-melanotropin stimulating hormone analog which has integrally located a radionuclide. The radionuclide is administered to the body in an amount sufficient to allow uptake and retention by the tumor cells.

Melanotropin analogs for potential radiopharmaceuticals for diagnosis and treatment of melanoma

Melanotropin analogs for potential radiopharmaceuticals for diagnosis and treatment of melonoma

Growing community of inventors

Columbia, MO, United States of America

Thomas P Quinn