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    TORROIDAL MESOPOROUS SILICA NANOPARTICLES (TMSNPS) AND RELATED PROTOCELLS
    1.
    发明申请
    TORROIDAL MESOPOROUS SILICA NANOPARTICLES (TMSNPS) AND RELATED PROTOCELLS 有权
    微生物多糖二氧化硅纳米粒子（TMSNPS）及相关方法

    公开(公告)号：US20160338954A1

    公开(公告)日：2016-11-24

    申请号：US15023110

    申请日：2014-09-18

    Applicant: STC. UNM ,  SANDIA CORPORATION

    Inventor： C. Jeffrey Brinker ,  Yu-Shen Lin

    IPC: A61K9/127 ,  A61K38/16 ,  C12N15/88 ,  A61K39/395 ,  A61K9/51 ,  A61K31/7088 ,  A61K38/43

    CPC classification number: A61K9/1271 ,  A61K9/14 ,  A61K9/5115 ,  A61K9/5123 ,  A61K31/7088 ,  A61K38/16 ,  A61K38/43 ,  A61K39/395 ,  B82Y5/00 ,  B82Y15/00 ,  C12N15/88

    Abstract: In one aspect, the invention provides novel monodisperse, colloidally-stable, torroidal mesoporous silica nanoparticles (TMSNPs) which are synthesized from ellipsoid-shaped mesoporous silica nanoparticles (MSNPs) which are prepared using an ammonia base-catalyzed method under a low surfactant conditions. Significantly, the TMSNPs can be loaded simultaneously with a small molecule active agent, a siRNA, a mRNA, a plasmid and other cargo and can be used in the diagnosis and/or treatment of a variety of disorders, including a cancer, a bacterial infection and/or a viral infection, among others. Related protocells, pharmaceutical compositions and therapeutic and diagnostic methods are also provided.

    Abstract translation: 一方面，本发明提供了由在低表面活性剂条件下使用氨碱催化法制备的椭圆形介孔二氧化硅纳米粒子（MSNP）合成的新型单分散，胶体稳定的环形介孔二氧化硅纳米粒子（TMSNP）。 值得注意的是，TMSNPs可以与小分子活性剂，siRNA，mRNA，质粒和其他货物同时加载，并且可以用于诊断和/或治疗各种疾病，包括癌症，细菌感染 和/或病毒感染等。 还提供了相关的原细胞，药物组合物和治疗和诊断方法。

    POROUS NANOPARTICLE-SUPPORTED LIPID BILAYERS (PROTOCELLS) FOR TARGETED DELIVERY AND METHODS OF USING SAME
    4.
    发明申请
    POROUS NANOPARTICLE-SUPPORTED LIPID BILAYERS (PROTOCELLS) FOR TARGETED DELIVERY AND METHODS OF USING SAME 审中-公开

    公开(公告)号：US20190091150A1

    公开(公告)日：2019-03-28

    申请号：US16025557

    申请日：2018-07-02

    Applicant: STC.UNM ,  Sandia Corporation

    Inventor： C. Jeffrey Brinker ,  Eric C. Carnes ,  Carlee Erin Ashley ,  Cheryl L. Willman

    IPC: A61K9/127 ,  A61K31/704 ,  A61K33/24 ,  A61K47/69 ,  C07K14/47 ,  A61K45/06 ,  A61K47/62 ,  C12N15/88 ,  A61K39/05 ,  C12N15/113 ,  A61K31/711 ,  A61K48/00 ,  A61K38/00

    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.

    Cell-Based Composite Materials with Programmed Structures and Functions
    6.
    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

    Applicant: Sandia Corporation ,  STC.UNM

    Inventor： Bryan J. Kaehr ,  C. Jeffrey Brinker ,  Jason L. Townson

    IPC: C12N11/14

    CPC classification number: G01N1/2806 ,  C08K3/36 ,  C12N11/14 ,  G01N1/2853

    Abstract: 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.

    Abstract translation: 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
    8.
    发明授权
    Porous nanoparticle-supported lipid bilayers (protocells) for targeted delivery and methods of using same 有权

    公开(公告)号：US10022327B2

    公开(公告)日：2018-07-17

    申请号：US14970998

    申请日：2015-12-16

    Applicant: STC.UNM ,  SANDIA CORPORATION

    Inventor： C. Jeffrey Brinker ,  Eric C. Carnes ,  Carlee Erin Ashley ,  Cheryl L. Willman

    IPC: A61K9/127 ,  A61K31/704 ,  A61K31/711 ,  A61K33/24 ,  A61K39/05 ,  C12N15/113 ,  C07K14/47 ,  C12N15/88 ,  A61K45/06 ,  A61K47/62 ,  A61K47/69 ,  A61K38/00 ,  A61K48/00

    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.

    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

    Applicant: Sandia Corporation ,  STC.UNM

    Inventor： Bryan J. Kaehr ,  C. Jeffrey Brinker ,  Jason L. Townson

    IPC: C12N11/14

    CPC classification number: G01N1/2806 ,  C08K3/36 ,  C12N11/14 ,  G01N1/2853

    Abstract: 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.

    Abstract translation: 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。

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