Cornell University

Memorial Sloan Kettering Cancer Center

Sloan-Kettering Institute for Cancer Research

Yale University

Other

University of Missouri

Quest Medical Imaging B.v

Larson, Daniel E.

Wiesner, Ulrich B.

Webb, Watt W.

Ow, Hooisweng

Ulrich B Wiesner

Michelle S Bradbury

Kai Ma

Jason S Lewis

Steven M Larson

Andrew A Burns

Joerg G Werner

Barney Yoo

Oula Penate Medina

Snehal G Patel

Hooisweng Ow

Rachel M Dorin

Howard Scher

William Anthony Phillip

Thomas P Quinn

Joshua A Hinckley

Feng Chen

Daniella Karassawa Zanoni

Michael Overholtzer

Michael O Thompson

Carlos M Garcia

Francis J DiSalvo

Carlo D Montemagno

Erik Herz

Kwan Wee Tan

Carlie Mendoza

Lilit L Yeghiazarian

Nadeem R Abu-Rustum

Richard J C Meester

Qi Zhang

Mohan Pauliah

Yuk Mun Li

Peiming Chen

Watt W Webb

Héctor D Abruña

Byungki Jung

Scott C Warren

Lara A Estroff

Gabriel G Rodriguez-Calero

Wolfgang Weber

Hitesh Arora

Ferdinand F E Kohle

Yusuke Hibi

Nikhil Dhawan

Hoosweng Ow

Ferdinand Fe Kohle

Mahendra Christopher Orilall

Nirmalya Bag

Jacob Erstling

Thomas C Gardinier

Brian Madajewski

Jinwoo Lee

Daniel R Larson

Karim Touijer

Hiroaki Sai

Tara C Zedayko

Ralph Ulrich

Josef W Zwanziger

Susan De Paul

Hans Wolfgang Spiess

David T Moore

Srikant K Iyer

Andrew Burns

Tom Quinn

Medina Oula Penate

Described is a versatile surface modification approach to, for example, modularly and orthogonally functionalize nanoparticles (NPs) such as, for example, PEGylated nanoparticles, ith various types of different functional ligands (functional groups) on the NP surface. It enables the synthesis of, for example, penta-functional PEGylated nanoparticles integrating a variety of properties into a single NP, e.g., fluorescence detection, specific cell targeting, radioisotope chelating/labeling, ratiometric pH sensing, and drug delivery, while the overall NP size remains, for example, below 10 nm.

Functionalized nanoparticles and methods of making and using same

Asymmetric films, methods of making asymmetric films, and uses of asymmetric films. A method may include using at least two different solvents and at least one homopolymer and at least one block copolymer that can undergo self assembly, where the solvents are immiscible and have different surface tension, where, on film formation, all or substantially all of the block copolymer(s) migrate to an exterior surface of the homopolymer. The asymmetric films may include an isoporous region or layer and an asymmetric region or layer, where the asymmetric region does not include 10 percent by weight or more of the multiblock copolymer(s) and/or the isoporous region/layer and the asymmetric pore region/layer are not independently (or separately) formed and/or not laminated together to form the asymmetric film. The films can be used in devices, such as, for example, filtration devices.

Asymmetric multiblock copolymer-homopolymer films, methods of making same, and uses thereof

Provided are sulfur- or heavy atom-containing silica or aluminosilica nanoparticles. A nanoparticle can have at least one dye molecule covalently bonded to the silica or aluminosilica matrix of the silica or aluminosilica nanoparticle, respectively. The nanoparticle may have a size, such as, for example, a longest dimension, of less than 10 nm. The silica or aluminosilica nanoparticle can be used in methods such as, for example, imaging methods and photodynamic therapy methods. The imaging methods can provide sub-diffraction limit resolution.

Sulfur- or heavy atom-containing nanoparticles, methods of making same, and uses thereof

Described herein are systems and methods for particle-based photodynamic therapy (PDT) for the treatment of diseases such as cancer of the oral cavity and/or ovarian cancer metastases along the lining of the pelvis. The technology includes an imaging system (e.g., a multichannel imaging camera) configured to perform diagnostic and/or therapeutic treatment on diseased tissue. In certain embodiments, the imaging system comprises one or more excitation sources (e.g., one or more lasers) to assess and/or treat diseased tissue.

Nanotherapeutic systems and methods using particle-driven photodynamic therapy (PDT)

The present disclosure provides methods of analyzing and/or purifying inorganic nanoparticles that may be functionalized with one or more dye group. Analyzing and/or purifying the inorganic nanoparticles includes utilizing liquid chromatography, such as, for example, high performance liquid chromatography (HPLC). Methods of the present disclosure may be used to determine the location of one or more dye groups on and/or in the inorganic nanoparticles. The present disclosure also provides methods of making inorganic nanoparticles and compositions of inorganic nanoparticles.

Ultrasmall nanoparticles and methods of making, using and analyzing same

Methods of obtaining and kits that can be used to obtain an optical super-resolution image of a sample or a portion thereof or an individual or a portion thereof. In various examples, the individual is an individual with cancer. In various examples, a method includes contacting a sample or individual with one or more aluminosilicate nanoparticle(s) that have at least one organic fluorophore molecule covalently bonded to the aluminosilicate network of the nanoparticle(s), or a composition including the aluminosilicate nanoparticle(s); irradiating the sample or the individual, thereby exciting at least one of the fluorophore molecules of an individual aluminosilicate nanoparticle; and obtaining a fluorescence image or a sequence of fluorescence images, which can be processed to obtain a super-resolution image of the sample or the individual. In various examples, the sample is a biological sample, living or fixed tissues and/or cells, or a biopsy obtained from an individual.

Super-resolution optical microscopy using aluminosilicate nanoparticles

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

An aqueous synthesis methodology for the preparation of silica nanoparticles (SNPs), core-shell SNPs having, for example, a size of 2 to 15 nm and narrow size-dispersion with size control below 1 nm, i.e. at the level of a single atomic layer. Different types of dyes, including near infrared (NIR) emitters, can be covalently encapsulated within and brightness can be enhanced via addition of extra silica shells. The surface may be functionalized with polyethylene glycol (PEG) groups and, optionally, specific surface ligands. This aqueous synthesis methodology also enables synthesis of 2 to 15 nm sized fluorescent core and core-shell aluminosilicate nanoparticles (ASNPs) which may also be surface functionalized. Encapsulation efficiency and brightness of highly negatively charged NIR fluorophores is enhanced relative to the corresponding SNPs without aluminum.

Ultrasmall nanoparticles and methods of making and using same

Presented herein is a multichannel imaging system capable of detecting and distinguishing multiple fluorescent light sources simultaneously. Also described herein are methods of using the system to image disease or cellular abnormalities, e.g., for diagnostic and/or intraoperative purposes.

Systems, methods, and apparatus for multichannel imaging of fluorescent sources in real-time

A method for forming an isoporous graded film comprising multiblock copolymers and isoporous graded films. The films have a surface layer and a bulk layer. The surface layer can have at least 1×10pores/mand a pore size distribution (d/d)) of less than 3. The bulk layer has an asymmetric structure. The films can be used in filtration applications.

Multiblock copolymer films, methods of making same, and uses thereof

Described herein is a method of induced cell death via ferroptosis by nanoparticle ingestion. Moreover, the present disclosure describes the administration of high concentrations of ultrasmall nanoparticles at multiple times over the course of treatment in combination with a nutrient-depleted environment, thereby modulating cellular metabolic pathways to induce cell death by the mechanism ferroptosis. Ferroptosis involves iron, reactive oxygen species, and a synchronous mode of cell death execution.

Methods of treatment using ultrasmall nanoparticles to induce cell death of nutrient-deprived cancer cells via ferroptosis

A method providing direct access to porous three-dimensionally (3D) continuous polymer network structures and shapes by combining BCP-resol co-assembly with COlaser-induced transient heating. The COlaser source transiently heats the BCP-directed resol hybrid films to high temperatures at the beam position, inducing locally controlled resol thermopolymerization and BCP decomposition in ambient conditions. This enables shaping of BCP-directed porous resin structures with tunable 3D interconnected pores in a single process. Pore size can be varied from 10 nm to about 600 nm.

Porous resin structures

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

Described herein are nanoprobes comprising ultrasmall aminated and cRGDY-conjugated nanoparticles labeled with Zirconium-89 (Zr) and methods of their use. The provided compositions are renally clearable and possess suitable blood circulation half-time, high tumor active targeting capability, dominant renal clearance, low liver accumulation, and a high tumor-to-background ratio. The described nanoprobes exhibit great potential as 'target-or-clear' tracers to human subjects for systemic targeted imaging (or treatment) of cancer.

Ultrasmall nanoparticles labeled with Zirconium-89 and methods thereof

A method for forming an isoporous graded film comprising multiblock copolymers and isoporous graded films. The films have a surface layer and a bulk layer. The surface layer can have at least 1&#xd7;10pores/mand a pore size distribution (d/d)) of less than 3. The bulk layer has an asymmetric structure. The films can be used in filtration applications.

Growing community of inventors

Ithaca, NY, United States of America

Ulrich B Wiesner