Porous nanoparticle-supported lipid bilayers (protocells) for targeted delivery including transdermal delivery of cargo and methods thereof

Patent metadata

Field	Value
Publication number	US-2017232115-A1
Application number	US-201615380962-A
Country	US
Kind code	A1
Filing date	Dec 15, 2016
Priority date	Oct 14, 2011
Publication date	Aug 17, 2017
Grant date	—

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.

First claim

What is claimed is:

1 . A cell-targeting pon:.ms protocell comprising:
nanoponms silica or metal oxide core with a supported lipid bilayer and at least one further component selected from the group consisting of a cell targeting species; a fusogenic peptide that promotes endosomal escape of protooells and encapsulated DNA, and other cargo comprising at least one cargo component selected from the group consisting of double stranded linear DNA; plasmid DNA; drug an imaging agent, small interfering RNA, small hairpin RNA, mieroRNA, or a mixture thereof, wherein one, of said cargo components is optionally conjugated further with a nuclear localization sequence.

Assignees

• Stc Unm
• Sandia Corp

Inventors

• Ashley Carlee Erin
• Brinker C Jeffrey
• Carnes Eric C
• Fekrazad Mohammed Houman
• Felton Linda A
• Negrete Oscar
• Padilla David Patrick
• Wilkinson Brian S
• Wilkinson Dan C
• Willman Cheryl L

Classifications

• A61P31/12

  Antivirals · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P35/02

  specific for leukemia · CPC title

• C12Y204/02036

  NAD(+)--diphthamide ADP-ribosyltransferase (2.4.2.36) · CPC title

• A61K31/704

  attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)} · CPC title