The General Hospital Corporation

University of Massachusetts

Pharmain Corporation

The General Hospital Corporation Massachusetts

Alexei A Bogdanov

Ralph Weissleder

Ching-Hsuan Tung

Lee Josephson

Umar Mahmood

Thomas J Brady

Gerardo M Castillo

Elijah M Bolotin

Paul C Zamecnik

David R Tabatadze

Pallab Banerjee

John W Chen

Manel Querol

Valeriy Metelev

Wilfried Reichardt

Ronald Callahan

There is provided a method of preparing nanoparticles and novel nanoparticles. The nanoparticle preparation comprises the generation of a mixture comprising a plurality of metal-containing compounds and a copolymer of a polyethylene glycol and an amine-containing polyamino acid such as polylysine where a metal core and polymer shell nanoparticle is formed. The novel nanoparticles have a metallic core and a graft copolymer shell of polyethylene glycol and an amine-containing polyamino acid where the shell least partially surrounds the metallic core and is non-ionically bound to the metallic core via metal-amine bonds.

Graft-copolymer stabilized metal nanoparticles

The present invention relates, in part, to an oligonucleotide-core carrier comprising a carrier, and oligonucleotide groups covalently linked to the carrier. The oligonucleotide groups are capable of dissociably linking load molecules such as therapeutic agents. The oligonucleotide-core carrier may also comprise protective side chains, and targeting molecules.

Oligonucleotide core carrier compositions for delivery of nucleic acid-containing therapeutic agents, methods of making and using the same

An intramolecularly-quenched, near infrared fluorescence probe that emits substantial fluorescence only after interaction with a target tissue (i.e., activation) is disclosed. The probe includes a polymeric backbone and a plurality of near infrared fluorochromes covalently linked to the backbone at fluorescence-quenching interaction-permissive positions separable by enzymatic cleavage at fluorescence activation sites. The probe optionally includes protective chains or fluorochrome spacers, or both. Also disclosed are methods of using the intramolecularly-quenched, near infrared fluorescence probes for in vivo optical imaging.

Intramolecularly-quenched near infrared fluorescent probes

This invention relates to biochemistry and magnetic resonance imaging.

Imaging of enzyme activity

Described are phosphoramidite nucleoside analog monomers, precursors thereof, and oligonucleotides including one or more of the monomers. The monomers can be used during automated synthesis of oligonucleotide derivatives, and allow for incorporation of one or several reporter groups, organic molecules, bio-molecules, small molecules or other chemical groups at the internucleoside phosphotriesters. Oligonucleotides including the monomers have a number of uses in therapeutic, diagnostic, and research applications.

Phosphoramidite nucleoside analogs

Hyperbranched dendron (HD) polymers are synthesized using low molecular weight polyethyleneimine (BPEI-L) as a core and used for gene delivery. The obtained polymers display low toxicity and efficient gene delivery at low nitrogen-to-phosphate (N/P) ratios. Using successive attachment of ethyleneimine moieties to a PEI core, the polymer has a lower relative ratio of linear-to-branched structures than in the core PEI. The more extensive branching enables the polymer to condense plasmid DNA into nanostructure complexes with a size of less than or equal to about 100 nm. The complexes are stable and efficient in transfecting cells in the presence of serum. Bioluminescent imaging of in vivo gene expression using a luciferase reporter gene performed in live mice showed gene expression in the liver and in submandibular lymph nodes.

Hyperbranched dendron and methods of synthesis and use thereof

The invention features methods of detecting enzymatic activity (e.g., in a magnetic resonance image). In general, the methods include: (1) providing a monomeric substrate (e.g., a substrate that is polymerizable in the presence of an enzyme or as a result of an enzyme-catalyzed reaction), having the generic structure X-Y-Z, where X includes a chelator moiety having a chelated paramagnetic or superparamagnetic metal atom or ion, Y includes a linker moiety (e.g., to provide a covalent or non-covalent chemical bond or bonds between X and Z), and Z includes a polymerizing moiety; (2) contacting the substrate with a target tissue, wherein the substrate undergoes polymerization to form a paramagnetic or superparamagnetic polymer, the polymerization being catalyzed by an enzyme in an extracellular matrix or bound to the surfaces of cells of the target tissue; and (3) detecting an increase in relaxivity for the polymer relative to an equivalent amount of unpolymerized substrate. The invention also features substrate compositions.

Imaging of enzymatic activity

Intramolecularly-quenched near infrared flourescent probes

Nucleic acid-imaging compositions and methods for noninvasive imaging of a nucleic acid introduced into somatic tissues of an animal or human are disclosed. The noninvasive imaging enables quantitative assessment of the biodistribution of the introduced nucleic acid. The disclosed imaging compounds include a base-binding moiety, a phosphate-binding moiety, and a metal-binding moiety. A chelated metal is non-invasively detected for imaging by radioactivity or magnetic resonance.

Noninvasive imaging of nucleic acid vectors

A biocompatible graft co-polymer adduct including a polymeric carrier, a protective chain linked to the polymeric carrier, a reporter group linked to the carrier or to the carrier and the protective chain, and a reversibly linked Pt(II) compound. The invention also relates to a method of treating a disease in a patient, particularly cancer, by administering to the patient a therapeutically effective amount of the adduct, and may include scanning the patient using an imaging technique which can provide a visible image of the distribution of the adduct.

Graft co-polymer adducts of platinum (II) compounds

The invention features a method of blood pool imaging which utilizes an imaging agent which can be easily labelled with a radioactive isotope and injected into a patient. The imaging agent is a covalent conjugate of a polymeric carrier, protective groups, and chelating groups. The imaging agent is preferably provided in the form of a blood pool imaging composition, which includes an imaging agent of the invention, a buffer and a reducing compound. A radioactive isotope is added to the blood pool imaging composition to label the imaging agent, and the composition containing the labelled imaging agent is injected intravenously into a patient.

Blood pool imaging composition and method of its use

A biocompatible medical composition including a polymeric carrier, a protective chain linked to the polymeric carrier, and a reporter group linked to the carrier or to the carrier and the protective chain. The invention also relates to a method of treating a disease in a patient by administering to the patient a therapeutically effective amount of the composition, and may include scanning the patient using an imaging technique which can detect the reporter group to obtain a visible image of the distribution of the composition.

Medical compositions

Biocompatible, biodegradable, hydrogels are prepared from a backbone bonded to a cross-linking agent. Suitable backbones include proteins and polysaccharides, e.g,, albumin, polymannuronic acid, or polygalacturonic acid. Suitable cross-linking agents include polyvalent derivatives of polyethylene or polyalkylene glycol. These hydrogel compositions may be loaded with diagnostic labels, e.g,, radiopaque, paramagnetic, or superparamagnetic materials, or therapeutic drugs, e.g., chemotherapeutic drugs, antibiotics, or cells that produce therapeutic agents. This invention also relates to methods of use of such hydrogels for imaging during interventional procedures of a patient.

Growing community of inventors

Westborough, MA, United States of America

Alexei A Bogdanov