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    UNIVERSAL MULTI-FUNCTIONAL GSH-RESPONSIVE SILICA NANOPARTICLES FOR DELIVERY OF BIOMOLECULES INTO CELLS
    3.
    发明申请
    UNIVERSAL MULTI-FUNCTIONAL GSH-RESPONSIVE SILICA NANOPARTICLES FOR DELIVERY OF BIOMOLECULES INTO CELLS 有权

    公开(公告)号：US20220105202A1

    公开(公告)日：2022-04-07

    申请号：US17501635

    申请日：2021-10-14

    申请人： Wisconsin Alumni Research Foundation

    发明人： Shaoqin GONG ,  Yuyuan Wang

    IPC分类号： A61K48/00 ,  A61K9/51 ,  A61K47/69 ,  A61P25/00 ,  C08G83/00

    摘要： The present technology provides a nanoparticle comprising: the polysiloxanes comprise silyloxy subunits having the structure (I) as shown herein, wherein Ra at each occurrence is independently selected from a bond to a Si of another polysiloxane chain or a C1-12 alkyl group; Ri at each occurrence is independently selected from the group consisting of C1-12 alkyl and C2-12 alkenyl groups, optionally substituted with a substituent selected from the group consisting of halogen and NR12, wherein each occurrence of R1 is independently selected from H or a C1-12 alkyl group, or two R1 groups, together with the N atom to which they are attached, form a pyrrolidine or piperidine ring; the crosslinks between polysiloxanes comprise disulfide linkages, the nanoparticle comprises an exterior surface comprising surface-modifying groups attached to and surrounding the silica network, wherein the surface-modifying groups comprise polyethylene glycol (PEG), polysarcosine, polyzwitterion, polycation, polyanion, or combinations of two or more thereof; and the nanoparticle has an average diameter of 15 nm to 200 nm. The nanoparticles herein may include biomolecules such as polynucleic acids, proteins, and complexes thereof, e.g., Cas9 RNP.

    POLYPLEX DELIVERY SYSTEM FOR PROTEINS, NUCLEIC ACIDS AND PROTEIN/NUCLEIC ACID COMPLEXES
    4.
    发明申请
    POLYPLEX DELIVERY SYSTEM FOR PROTEINS, NUCLEIC ACIDS AND PROTEIN/NUCLEIC ACID COMPLEXES 审中-公开

    公开(公告)号：US20190307888A1

    公开(公告)日：2019-10-10

    申请号：US16282174

    申请日：2019-02-21

    申请人： Wisconsin Alumni Research Foundation

    发明人： Shaoqin GONG ,  Yuyuan WANG ,  Krishanu SAHA ,  Amr Ashraf ABDEEN

    IPC分类号： A61K47/59 ,  A61K47/61 ,  A61K49/00 ,  A61K51/06 ,  A61K38/46 ,  A61K31/7105

    摘要： Provided herein are nanoplexes comprising a payload selected from a protein and/or a polynucleic acid; and a plurality of copolymers comprising a first copolymer that is poly(N,N′-bis(acryloyl)cystamine-poly(aminoalkyl)) (PBAP), a second copolymer that is poly(C2-3 akylene glycol)-PBAP-poly(C2-3 akylene glycol), and a third copolymer that is TG-poly(C2-3 akylene glycol)-PBAP-poly(C2-3 akylene glycol)-TG wherein TG at each occurrence is independently a targeting ligand, a cell penetrating peptide, an imaging agent or a capping group, provided that a plurality of TG groups is a targeting ligand; wherein the payload is non-covalently complexed to one or more of the copolymers, one or more of the first, second, and/or third copolymers comprises an endosomal escape group having a pKa of about 4.5 to about 6.5, and optionally one or more of the first, second, and/or third copolymers comprises a host and a guest non-covalent crosslinker.

    UNIMOLECULAR NANOPARTICLES FOR EFFICIENT DELIVERY OF THERAPEUTIC RNA
    5.
    发明申请
    UNIMOLECULAR NANOPARTICLES FOR EFFICIENT DELIVERY OF THERAPEUTIC RNA 有权

    公开(公告)号：US20210346309A1

    公开(公告)日：2021-11-11

    申请号：US17331012

    申请日：2021-05-26

    申请人： Wisconsin Alumni Research Foundation

    发明人： Shaoqin GONG ,  Guojun CHEN

    IPC分类号： A61K9/51 ,  A61K31/713 ,  A61P35/00

    摘要： Provided are a unimolecular nanoparticle, a composition thereof, and methods of use thereof, and includes 1) a dendritic polymer having a molecular weight of about 500-120,000 Da and terminating in hydroxyl, amino or carboxylic acid groups; 2) cationic polymers attached to at least a majority of the terminating groups of the dendritic polymer via a pH-sensitive linker, wherein each cationic polymer comprises a polymeric backbone attached to cationic functional groups and to weakly basic groups by disulfide bonds, wherein the molar ratio of cationic functional groups to weakly basic groups ranges from 1:1-5:1, and has a molecular weight from about 1,000-5,000 Da; and 3) poly(ethylene glycol) attached to a plurality of cationic polymers and having a terminal group selected from a targeting ligand, OH, O-alkyl, NH2 , biotin, or a dye, wherein the terminal group of at least one poly(ethylene glycol) is having a molecular weight of about 1,000-15,000 Da.

    PERIVASCULAR DRUG DELIVERY SYSTEM
    7.
    发明申请
    PERIVASCULAR DRUG DELIVERY SYSTEM 审中-公开

    公开(公告)号：US20180042844A1

    公开(公告)日：2018-02-15

    申请号：US15674293

    申请日：2017-08-10

    申请人： Wisconsin Alumni Research Foundation

    发明人： K. Craig KENT ,  Shaoqin GONG ,  Xudong SHI ,  Guojun CHEN ,  Lian-Wang GUO

    IPC分类号： A61K9/107 ,  A61K31/436 ,  A61K47/34 ,  A61K9/06

    CPC分类号： A61K9/1075 ,  A61K9/06 ,  A61K9/5146 ,  A61K9/5153 ,  A61K31/436 ,  A61K47/34

    摘要： The present technology provide compositions that are drug delivery systems for the sustained release of anti-stenotic drugs for the treatment and prevention of occlusion of blood vessels, particularly after perivascular surgery. The compositions include a hydrogel, unimolecular micelles dispersed within the hydrogel, and an effective amount of anti-stenotic drug dispersed within the unimolecular micelle. The hydrogel may be a di-or tri-block copolymer comprising one block of poly(ethylene glycol) (PEG) and one or two blocks of poly(lactic-co-glycolic acid) (PLGA). The unimolecular micelle may include three domains: a dendritic polymer core, hydrophobic block polymers (e.g., PVL, PVCL, and/or PCL) attached to the core and PEG attached to the hydrophobic block polymers.

    pH-RESPONSIVE SILICA METAL ORGANIC FRAMEWORK NANOPARTICLES FOR DELIVERY OF BIOACTIVE MOLECULES
    10.
    发明申请
    pH-RESPONSIVE SILICA METAL ORGANIC FRAMEWORK NANOPARTICLES FOR DELIVERY OF BIOACTIVE MOLECULES 有权

    公开(公告)号：US20220177494A1

    公开(公告)日：2022-06-09

    申请号：US17602239

    申请日：2020-04-08

    申请人： Wisconsin Alumni Research Foundation

    发明人： Shaoqin GONG ,  Yuyuan WANG

    IPC分类号： C07F3/06 ,  A61K47/69 ,  A61K31/704 ,  A61K9/51 ,  A61K9/00

    摘要： Provided herein are silica metal organic framework (SMOF) nanoparticles that are pH-responsive for delivery of bioactive molecules. The nanoparticles include a organosilica network comprising a plurality of imidazolyl and/or carboxyl groups; a metal organic framework component comprising a transition metal coordinated to a coordinating ligand, wherein the transition metal is selected from the group consisting of zinc, iron, zirconium, copper, and cobalt, and the coordinating ligand is selected from an imidazolate ligand or a carboxylate ligand; a bioactive payload selected from the group consisting of a hydrophilic drug, a polynucleic acid, a protein and a protein-polynucleic acid complex; and a surface-modifying polymer conjugated to the same or a different organosilica network and forming at least part of an exterior surface of the nanoparticle, wherein the surface-modifying polymer is selected from polyethylene glycol and/or a polyzwitterion; and wherein the zinc also coordinates the imidazolyl or carboxyl group of the organosilica network.