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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:
; ; ;
Publication Date:
Research Org.:
Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1345394
Patent Number(s):
9,579,283
Application Number:
14/113,371
Assignee:
STC.UNM SNL-A
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

Citation Formats

Brinker, C. Jeffrey, Carnes, Eric C., Ashley, Carlee Erin, and Willman, Cheryl L. Porous nanoparticle-supported lipid bilayers (protocells) for targeted delivery and methods of using same. United States: N. p., 2017. Web.
Brinker, C. Jeffrey, Carnes, Eric C., Ashley, Carlee Erin, & Willman, Cheryl L. Porous nanoparticle-supported lipid bilayers (protocells) for targeted delivery and methods of using same. United States.
Brinker, C. Jeffrey, Carnes, Eric C., Ashley, Carlee Erin, and Willman, Cheryl L. Tue . "Porous nanoparticle-supported lipid bilayers (protocells) for targeted delivery and methods of using same". United States. doi:. https://www.osti.gov/servlets/purl/1345394.
@article{osti_1345394,
title = {Porous nanoparticle-supported lipid bilayers (protocells) for targeted delivery and methods of using same},
author = {Brinker, C. Jeffrey and Carnes, Eric C. and Ashley, Carlee Erin and Willman, Cheryl L.},
abstractNote = {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 cancer treatment and drug discovery.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = {Tue Feb 28 00:00:00 EST 2017},
month = {Tue Feb 28 00:00:00 EST 2017}
}

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