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POLYPLEX DELIVERY SYSTEM FOR PROTEINS, NUCLEIC ACIDS AND PROTEIN/NUCLEIC ACID COMPLEXES

机译:用于蛋白质,核酸和蛋白质/核酸复合物的多聚体递送系统

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.
机译:本文提供了纳米复合物,其包含选自蛋白质和/或多核酸的有效载荷;以及包含第一共聚物的多种共聚物,所述第一共聚物为聚(N,N'-双(丙烯酰基)胱胺-聚(氨基烷基))(PBAP),第二共聚物为聚(C 2-3 丙二醇)-PBAP-聚(C 2-3 烷二醇),以及第三种共聚物,TG-聚(C 2-3 烷二醇)-PBAP -聚(C 2-3 亚烷基二醇)-TG,其中每次出现的TG独立为靶向配体,细胞穿透肽,显像剂或加帽基团,条件是多个TG基团是靶向配体;其中有效载荷与一种或多种共聚物非共价复合,第一,第二和/或第三共聚物中的一种或多种包含pKa为约4.5至约6.5的内体逸出基团,并可选地包含一个或多个第一种,第二种和/或第三种共聚物中的一种包含主体和客体非共价交联剂。

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