ASHLEY, CARLEE ERIN,BRINKER, C., JEFFREY,CARNES, ERIC C.,FEKRAZAD, MOHAMMAD HOUMAN,FELTON, LINDA A,NEGRETE, OSCAR,PADILLA, DAVID PATRICK,WILKINSON, BRIAN S,WILKINSON, DAN C,WILLMAN, CHERYL L
申请号：
MX2014004415
公开号：
MX2014004415A
申请日:
2012.10.12
申请国别(地区):
MX
年份:
2015
代理人:
摘要：
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.La presente invención se refiere a protocélulas específicamente dirigidas a la células de cáncer hepatocelular y a otras células cancerosas, las cuales comprenden un núcleo de sílice nanoporoso que soporta una bicapa lipídica al menos un agente que facilita la muerte de la célula cancerosa (como la tradicional molécula pequeña), una carga macromolecular (por ejemplo, ARNsi o una toxina proteica como la cadena A de la toxina ricina o la cadena A de la toxina diftérica) y/o un ADN plasmídico empaquetado con histona dispuesto dentro del núcleo de sílice nanoporoso (de preferencia, superenrollado para empaquetar con más eficiencia el ADN
