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    POROUS NANOPARTICLE-SUPPORTED LIPID BILAYERS (PROTOCELLS) FOR TARGETED DELIVERY AND METHODS OF USING SAME
    3.
    发明申请
    POROUS NANOPARTICLE-SUPPORTED LIPID BILAYERS (PROTOCELLS) FOR TARGETED DELIVERY AND METHODS OF USING SAME 审中-公开
    用于定向输送的多孔纳米脂质载体（PROTOCELLS）及其使用方法

    公开(公告)号：WO2012149376A2

    公开(公告)日：2012-11-01

    申请号：PCT/US2012/035529

    申请日：2012-04-27

    Applicant: STC.UNM ,  SANDIA CORPORATION ,  BRINKER, Jeffrey, C. ,  CARNES, Eric, C. ,  ASHLEY, Carlee, Erin

    Inventor： BRINKER, Jeffrey, C. ,  CARNES, Eric, C. ,  ASHLEY, Carlee, Erin

    IPC: A61K9/16 ,  A61K47/48 ,  A61K47/30 ,  A61K38/17 ,  A61K48/00

    CPC classification number: A61K9/1271 ,  A61K31/704 ,  A61K31/711 ,  A61K33/24 ,  A61K38/00 ,  A61K39/05 ,  A61K45/06 ,  A61K47/62 ,  A61K47/6901 ,  A61K48/0016 ,  C07K14/47 ,  C12N15/1135 ,  C12N15/88 ,  C12N2310/14 ,  C12N2320/32 ,  C12N2810/40

    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.

    Abstract translation: 本发明涉及用于特异性靶向肝细胞和其它癌细胞的原细胞，其包含具有支持的脂质双层的纳米多孔二氧化硅核心; 至少一种促进癌细胞死亡的药物（例如传统的小分子，大分子货物（例如siRNA或蛋白质毒素如蓖麻毒素A链或白喉毒素A链）和/或组蛋白包装的质粒DNA 设置在纳米多孔硅芯内（优选超螺旋以更有效地将DNA包装到原细胞中），其任选地用核定位序列修饰以帮助定位癌细胞核内的原细胞，以及表达参与治疗的肽的能力 （凋亡/细胞死亡）或作为报告物，靶向肽靶向待治疗的组织中的癌细胞，使得原细胞与靶细胞的结合是特异性和增强的，并且促进内源性逃逸的融合肽 原细胞和包封的DNA。根据本发明的原细胞可用于治疗癌症，特别是包括肝细胞（肝）癌症 选择性结合肝细胞组织或在癌症诊断中起作用的新型结合肽（c-MET肽），包括癌症治疗和药物发现。

    POROUS NANOPARTICLE-SUPPORTED LIPID BILAYERS (PROTOCELLS) FOR TARGETED DELIVERY AND METHODS OF USING SAME
    7.
    发明申请
    POROUS NANOPARTICLE-SUPPORTED LIPID BILAYERS (PROTOCELLS) FOR TARGETED DELIVERY AND METHODS OF USING SAME 审中-公开
    用于定向输送的多孔纳米脂质载体（PROTOCELLS）及其使用方法

    公开(公告)号：WO2012149376A3

    公开(公告)日：2013-01-17

    申请号：PCT/US2012035529

    申请日：2012-04-27

    Applicant: STC UNM ,  SANDIA CORP ,  BRINKER JEFFREY C ,  CARNES ERIC C ,  ASHLEY CARLEE ERIN

    Inventor： BRINKER JEFFREY C ,  CARNES ERIC C ,  ASHLEY CARLEE ERIN

    IPC: A61K9/16 ,  A61K38/17 ,  A61K47/30 ,  A61K47/48 ,  A61K48/00

    CPC classification number: A61K9/1271 ,  A61K31/704 ,  A61K31/711 ,  A61K33/24 ,  A61K38/00 ,  A61K39/05 ,  A61K45/06 ,  A61K47/62 ,  A61K47/6901 ,  A61K48/0016 ,  C07K14/47 ,  C12N15/1135 ,  C12N15/88 ,  C12N2310/14 ,  C12N2320/32 ,  C12N2810/40

    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.

    Abstract translation: 本发明涉及用于特异性靶向肝细胞和其它癌细胞的原细胞，其包含具有支持的脂质双层的纳米多孔二氧化硅核心; 至少一种促进癌细胞死亡的药物（例如传统的小分子，大分子货物（例如siRNA或蛋白质毒素如蓖麻毒素A链或白喉毒素A链）和/或组蛋白包装的质粒DNA 设置在纳米多孔硅芯内（优选超螺旋以更有效地将DNA包装到原细胞中），其任选地用核定位序列修饰以帮助定位癌细胞核内的原细胞，以及表达参与治疗的肽的能力 （凋亡/细胞死亡）或作为报告物，靶向肽靶向待治疗的组织中的癌细胞，使得原细胞与靶细胞的结合是特异性和增强的，并且促进内源性逃逸的融合肽 原细胞和包封的DNA。根据本发明的原细胞可用于治疗癌症，特别是包括肝细胞（肝）癌症 选择性结合肝细胞组织或在癌症诊断中起作用的新型结合肽（c-MET肽），包括癌症治疗和药物发现。

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