Title:
POROUS NANOPARTICLE-SUPPORTED LIPID BILAYERS (PROTOCELLS) FOR TARGETED DELIVERY INCLUDING TRANSDERMAL DELIVERY OF CARGO AND METHODS THEREOF
Document Type and Number:
WIPO Patent Application WO/2013/056132
Kind Code:
A3
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 cancer treatment and drug discovery.
Inventors:
ASHLEY CARLEE ERIN (US)
BRINKER C JEFFREY (US)
CARNES ERIC C (US)
FEKRAZAD MOHAMMAD HOUMAN (US)
FELTON LINDA A (US)
NEGRETE OSCAR (US)
PADILLA DAVID PATRICK (US)
WILKINSON BRIAN S (US)
WILKINSON DAN C (US)
WILLMAN CHERYL L (US)
BRINKER C JEFFREY (US)
CARNES ERIC C (US)
FEKRAZAD MOHAMMAD HOUMAN (US)
FELTON LINDA A (US)
NEGRETE OSCAR (US)
PADILLA DAVID PATRICK (US)
WILKINSON BRIAN S (US)
WILKINSON DAN C (US)
WILLMAN CHERYL L (US)
Application Number:
PCT/US2012/060072
Publication Date:
June 13, 2013
Filing Date:
October 12, 2012
Export Citation:
Assignee:
STC UNM (US)
SANDIA CORP (US)
SANDIA CORP (US)
International Classes:
A61K9/16; A61K31/7088; A61K31/7105; A61K33/24; A61K38/17; A61K47/48; A61K48/00; A61K49/08; A61K33/242; A61K33/243
Domestic Patent References:
| WO2010048572A1 | 2010-04-29 |
Foreign References:
| US20100255103A1 | 2010-10-07 |
Other References:
J. LIU ET AL.: "Porous Nanoparticle Supported Lipid Bilayers (Protocells) as Delivery Vehicle", JACS COMMUNICATIONS, vol. 131, 2009, pages 1354 - 1355, XP055029872
E.-M. KIM ET AL.: "Iodine 125-labeled mesenchymal epithelial transition factor binding peptide-click-cRGDyk heterodimer for glioma imaging", CANCER SCIENCE, vol. 102, no. 8, August 2011 (2011-08-01), pages 1516 - 1521, XP055074817
E.-M. KIM ET AL.: "Iodine 125-labeled mesenchymal epithelial transition factor binding peptide-click-cRGDyk heterodimer for glioma imaging", CANCER SCIENCE, vol. 102, no. 8, August 2011 (2011-08-01), pages 1516 - 1521, XP055074817
Attorney, Agent or Firm:
COLEMAN, Henry, D. (Bridgeport, CT, US)
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