摘要:
A method of controlling a physical characteristic of polymeric nanocarrier-encapsulated protein particles includes altering or selecting a weight percentage of a hydrophobic polymer block in a total amphiphilic diblock copolymer of a primary emulsion of a double emulsion, freeze-thaw technique. The primary emulsion is formed using a freeze-thaw cycle of the amphiphilic diblock copolymer and a protein having a molecular weight of up to or equal to 300,000 Da. Selection of the hydrophobic polymer block percentage alters one or more characteristics of the resulting nanoparticles, such as shape. Thus, as one aspect, a method of producing filamentous polymeric nanocarrier-encapsulated protein (i.e., active enzyme) particles involves forming a primary emulsion using a freeze-thaw cycle of (i) an amphiphilic diblock copolymer, which has a molecular weight of about 10,000 to about 100,000 Da and comprises a conjugate of the hydrophobic polymer block and a hydrophilic polymer block, wherein the amphiphilic diblock copolymer comprises greater than 81% to about 95% by weight of the hydrophobic polymer block; and a protein having a molecular weight of up to or equal to about 300,000 Da. Various compositions comprising such filamentous-shaped nanocarrier particles, and methods of use for diagnosis and therapy are disclosed.
摘要:
The invention provides a method for delivering a cargo molecule into a cell using a targeted DNA-based carrier (e.g., DNA dendrimer). Compositions and kits useful in the practice of the methods are also provided.
摘要:
Fusion proteins containing a ligand which specifically binds to a selected vascular bed linked to an anti-thrombotic molecule are provided. Also provided are methods for use of these fusion proteins to prevent coagulation, to dissolve blood clots and to protect against the risk of iatrogenic side effects including those arising from cancer therapy and specific vascular occluding agents.
摘要:
A method for enhancing intracellular delivery of effector molecules is provided. The method involves modifying selected antibodies with biotin and streptavidin, conjugating these antibodies with an effector molecule, and delivering the conjugated effector to an intracellular target specifically recognized by the antibody.
摘要:
Compositions are provided comprising a thrombomodulin domain linked to a targeting moiety that binds to a determinant on the surface of a target endothelial cell or red blood cell, wherein the thrombomodulin domain may be the extracellular domain, the N-terminal lectin-like domain, or an epidermal growth factor (EGF)-like domain. The targeting moiety may be a single chain antigen-binding domain (scFv), and the targeting moiety and thrombomodulin domain of the composition may be linked as a continuous polypeptide chain. Methods of delivery and use of a composition described herein are provided, as well as methods of treating or preventing thrombosis, inflammation, tissue ischemia, sepsis, acute lung injury (ALI), acute myocardial infarction (AMI), ischemic stroke, cerebrovascular disease, pulmonary embolism, or ischemic peripheral vascular disease is provided.
摘要:
The present invention is a method for encapsulating active protein in a polymeric nanocarrier. The instant method employs homogenization at subzero temperatures so that enzyme activity is retained. Enzymes which can be encapsulated by the present method include, for example, antioxidant enzymes and xenobiotic detoxifying enzymes. Encapsulation of an enzyme protects it from protease degradation and increases therapeutic half-life. Advantageously, polymeric nanoparticles of the invention are permeable to enzyme substrates and therefore enzymes encapsulated by the instant method can exert their effect without release from the nanocarrier. Methods for decomposing a reactive oxygen species, protecting against vascular oxidative stress, and detoxifying a xenobiotic are also provided.
摘要:
The present invention relates to compositions and methods for delivering lysosomal proteins. The compositions and methods described herein permit the targeted delivery of exogenous lysosomal proteins to cell surface proteins that allow their internalization via non-clathrin pathways. The present invention further relates to the use 10 of the compositions and methods for enzyme replacement therapy of lysosomal storage diseases. Nucleic acids, recombinant cells and kits useful for making and using the compositions of the invention are also provided.
摘要:
A multimolecular complex made up of a plasminogen activator conjugated to anti-ACE Mab 9B9 capable of delivering the plasminogen activator to the pulmonary endothelium is provided. Methods of using this complex to selectively deliver the plasminogen activator to the pulmonary endothelium to enhance fibrinolysis in the lungs of an animal are also provided. In addition, a method of prolonging the time a plasminogen activator is present in the circulation of an animal by conjugating the plasminogen activator to anti-ACE Mab 9B9 is also provided.
摘要翻译:提供了由能够将纤溶酶原激活剂递送至肺内皮的抗ACE Mab 9B9缀合的纤溶酶原激活物组成的多分子复合物。 还提供了使用该复合物选择性将纤溶酶原激活剂递送至肺内皮以增强动物肺部纤维蛋白溶解的方法。 此外,还提供了通过将纤溶酶原激活剂与抗ACE Mab 9B9缀合而延长纤维蛋白溶酶原激活剂在动物循环中的时间的方法。
摘要:
The present invention relates to compositions and methods for delivering lysosomal proteins. The compositions and methods described herein permit the targeted delivery of exogenous lysosomal proteins to cell surface proteins that allow their internalization via non-clathrin pathways. The present invention further relates to the use of the compositions and methods for enzyme replacement therapy of lysosomal storage diseases. Nucleic acids, recombinant cells and kits useful for making and using the compositions of the invention are also provided.
摘要:
Fusion proteins comprising a single chain antigen-binding domain (scFv) of a monoclonal antibody, linked to an anti-thrombotic agent, anti-inflammatory agent, or a pro-drug thereof are provided, where the polypeptide binds to a binding site (antigen) expressed on the surface of a red blood cell at a density greater than 5,000 copies per red blood cell. Pharmaceutical compositions comprising these fusion proteins, and methods of delivering an anti-thrombotic agent to the surface of a red blood cell via delivery of these fusion proteins, and methods of treating or preventing thrombosis, tissue ischemia, acute myocardial infarction (AMI), ischemic stroke, cerebrovascular disease, pulmonary embolism, or ischemic peripheral vascular disease via administration of the fusion proteins or compositions comprising same are also provided.