POROUS NANOPARTICLE-SUPPORTED LIPID BILAYERS (PROTOCELLS) FOR TARGETED DELIVERY AND METHODS OF USING SAME

    公开(公告)号:US20190091150A1

    公开(公告)日:2019-03-28

    申请号:US16025557

    申请日:2018-07-02

    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.

    Cell-Based Composite Materials with Programmed Structures and Functions
    3.
    发明申请
    Cell-Based Composite Materials with Programmed Structures and Functions 有权
    具有编程结构和功能的基于单元的复合材料

    公开(公告)号:US20160208238A1

    公开(公告)日:2016-07-21

    申请号:US14996048

    申请日:2016-01-14

    IPC分类号: C12N11/14

    摘要: The present invention is directed to the use of silicic acid to transform biological materials, including cellular architecture into inorganic materials to provide biocomposites (nanomaterials) with stabilized structure and function. In the present invention, there has been discovered a means to stabilize the structure and function of biological materials, including cells, biomolecules, peptides, proteins (especially including enzymes), lipids, lipid vesicles, polysaccharides, cytoskeletal filaments, tissue and organs with silicic acid such that these materials may be used as biocomposites. In many instances, these materials retain their original biological activity and may be used in harsh conditions which would otherwise destroy the integrity of the biological material. In certain instances, these biomaterials may be storage stable for long periods of time and reconstituted after storage to return the biological material back to its original form. In addition, by exposing an entire cell to form CSCs, the CSCs may function to provide a unique system to study enzymes or a cascade of enzymes which are otherwise unavailable.

    摘要翻译: 本发明涉及使用硅酸将生物材料(包括细胞结构)转化为无机材料以提供具有稳定结构和功能的生物复合材料(纳米材料)。 在本发明中,已经发现了稳定生物材料的结构和功能的手段,包括细胞,生物分子,肽,蛋白质(特别是酶),脂质,脂质囊泡,多糖,细胞骨架细丝,组织和器官与硅 酸,使得这些材料可以用作生物复合材料。 在许多情况下,这些材料保留其原始生物活性,并且可以在恶劣条件下使用,否则会破坏生物材料的完整性。 在某些情况下,这些生物材料可能长时间保持稳定,并在储存后重构,以将生物材料返回其原始形式。 此外,通过暴露整个细胞以形成CSCs,CSC可以起到提供独特的系统来研究否则不可用的酶或级联的酶。

    Porous nanoparticle-supported lipid bilayers (protocells) for targeted delivery and methods of using same

    公开(公告)号:US10022327B2

    公开(公告)日:2018-07-17

    申请号:US14970998

    申请日:2015-12-16

    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.

    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:US20160106671A1

    公开(公告)日:2016-04-21

    申请号:US14970998

    申请日:2015-12-16

    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.

    摘要翻译: 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,并且促进内体逃逸的融合肽 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。

    Cell-based composite materials with programmed structures and functions
    9.
    发明授权
    Cell-based composite materials with programmed structures and functions 有权
    具有编程结构和功能的基于单元的复合材料

    公开(公告)号:US09273305B1

    公开(公告)日:2016-03-01

    申请号:US13869799

    申请日:2013-04-24

    IPC分类号: C12N11/14

    摘要: The present invention is directed to the use of silicic acid to transform biological materials, including cellular architecture into inorganic materials to provide biocomposites (nanomaterials) with stabilized structure and function. In the present invention, there has been discovered a means to stabilize the structure and function of biological materials, including cells, biomolecules, peptides, proteins (especially including enzymes), lipids, lipid vesicles, polysaccharides, cytoskeletal filaments, tissue and organs with silicic acid such that these materials may be used as biocomposites. In many instances, these materials retain their original biological activity and may be used in harsh conditions which would otherwise destroy the integrity of the biological material. In certain instances, these biomaterials may be storage stable for long periods of time and reconstituted after storage to return the biological material back to its original form. In addition, by exposing an entire cell to form CSCs, the CSCs may function to provide a unique system to study enzymes or a cascade of enzymes which are otherwise unavailable.

    摘要翻译: 本发明涉及使用硅酸将生物材料(包括细胞结构)转化为无机材料以提供具有稳定结构和功能的生物复合材料(纳米材料)。 在本发明中,已经发现了稳定生物材料的结构和功能的手段,包括细胞,生物分子,肽,蛋白质(特别是酶),脂质,脂质囊泡,多糖,细胞骨架细丝,组织和器官与硅 酸,使得这些材料可以用作生物复合材料。 在许多情况下,这些材料保留其原始生物活性,并且可以在恶劣条件下使用,否则会破坏生物材料的完整性。 在某些情况下,这些生物材料可能长时间保持稳定,并在储存后重构,以将生物材料返回其原始形式。 此外,通过暴露整个细胞以形成CSCs,CSC可以起到提供独特的系统来研究否则不可用的酶或级联的酶。