Title: Porous nanoparticle-supported lipid bilayers (protocells) for targeted delivery and methods of using same

Abstract

The present invention is directed to protocells for specific targeting of hepatocellular and other cancer cells which comprise a nanoporous silica core with a supported lipid bilayer; at least one agent which facilitates cancer cell death (such as a traditional small molecule, a macromolecular cargo (e.g. siRNA or a protein toxin such as ricin toxin A-chain or diphtheria toxin A-chain) and/or a histone-packaged plasmid DNA disposed within the nanoporous silica core (preferably supercoiled in order to more efficiently package the DNA into protocells) which is optionally modified with a nuclear localization sequence to assist in localizing protocells within the nucleus of the cancer cell and the ability to express peptides involved in therapy (apoptosis/cell death) of the cancer cell or as a reporter, a targeting peptide which targets cancer cells in tissue to be treated such that binding of the protocell to the targeted cells is specific and enhanced and a fusogenic peptide that promotes endosomal escape of protocells and encapsulated DNA. Protocells according to the present invention may be used to treat cancer, especially including hepatocellular (liver) cancer using novel binding peptides (c-MET peptides) which selectively bind to hepatocellular tissue or to function in diagnosis of cancer, including cancermore » treatment and drug discovery. « less

Inventors:

Brinker, C. Jeffrey; Carnes, Eric C.; Ashley, Carlee Erin; Willman, Cheryl L.

Issue Date:

2017-02-28

Research Org.:

Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

Sponsoring Org.:

USDOE

OSTI Identifier:

1345394

Patent Number(s):

9579283

Application Number:

14/113,371

Assignee:

STC.UNM

Patent Classifications (CPCs):

A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61K - PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES

A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61P - SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

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A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61K - PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES

A61K31/704 - attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {
A61K31/711 - Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
A61K33/243 - Platinum
A61K38/00 - Medicinal preparations containing peptides
A61K39/05 - {Actinobacteria, e.g. Actinomyces, Streptomyces, Nocardia, Bifidobacterium, Gardnerella}, Corynebacterium
A61K45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K47/62 - the modifying agent being a protein, peptide or polyamino acid
A61K47/6901 - {Conjugates being cells, cell fragments, viruses, ghosts, red blood cells or viral vectors}
A61K48/0016 - {wherein the nucleic acid is delivered as a 'naked' nucleic acid, i.e. not combined with an entity such as a cationic lipid}
A61K9/1271 - {Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers

A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61P - SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

A61P31/14 - for RNA viruses
A61P31/18 - for HIV
A61P31/20 - for DNA viruses
A61P35/00 - Antineoplastic agents

C - CHEMISTRY C07 - ORGANIC CHEMISTRY C07K - PEPTIDES

C07K14/47 - from mammals

C - CHEMISTRY C12 - BIOCHEMISTRY C12N - MICROORGANISMS OR ENZYMES

C12N15/1135 - {against oncogenes or tumor suppressor genes}
C12N15/88 - using microencapsulation, e.g. using {amphiphile} liposome vesicle
C12N2310/14 - interfering N.A.
C12N2320/32 - Special delivery means, e.g. tissue-specific
C12N2810/40 - Vectors comprising a peptide as targeting moiety, e.g. a synthetic peptide, from undefined source

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DOE Contract Number:  

AC04-94AL85000

Resource Type:

Patent

Resource Relation:

Patent File Date: 2012 Apr 27

Country of Publication:

United States

Language:

English

Subject:

60 APPLIED LIFE SCIENCES; 59 BASIC BIOLOGICAL SCIENCES