Abstract: Temperature- and pH-responsive copolymer compositions, and drug delivery devices, conjugates, nanoparticles, and micelles that include the compositions.

Abstract: Compositions and methods for transport or release of therapeutic and diagnostic agents or metabolites or other analytes from cells, compartments within cells, or through cell layers or barriers are described. The compositions include a membrane barrier transport enhancing agent and are usually administered in combination with an enhancer and/or exposure to stimuli to effect disruption or altered permeability, transport or release. In a preferred embodiment, the compositions include compounds which disrupt endosomal membranes in response to the low pH in the endosomes but which are relatively inactive toward cell membranes (at physiologic pH, but can become active toward cell membranes if the environment is acidified below ca. pH 6.8), coupled directly or indirectly to a therapeutic or diagnostic agent. Other disruptive agents can also be used, responsive to stimuli and/or enhancers other than pH, such as light, electrical stimuli, electromagnetic stimuli, ultrasound, temperature, or combinations thereof.

Abstract: Compositions and methods for transport or release of therapeutic and diagnostic agents or metabolites or other analytes from cells, compartments within cells, or through cell layers or barriers are described. The compositions include a membrane barrier transport enhancing agent and are usually administered in combination with an enhancer and/or exposure to stimuli to effect disruption or altered permeability, transport or release. In a preferred embodiment, the compositions include compounds which disrupt endosomal membranes in response to the low pH in the endosomes but which are relatively inactive toward cell membranes (at physiologic pH, but can become active toward cell membranes if the environment is acidified below ca. pH 6.8), coupled directly or indirectly to a therapeutic or diagnostic agent. Other disruptive agents can also be used, responsive to stimuli and/or enhancers other than pH, such as light, electrical stimuli, electromagnetic stimuli, ultrasound, temperature, or combinations thereof.

Abstract: pH-Responsive polymer-based protein delivery carriers and compositions, methods for making the carriers and compositions, and methods for using the carriers and compositions for intracellular protein antigen delivery, inducing a cytotoxic T-lymphocyte response, introducing a tumor-specific protein antigen to an antigen presenting cell to induce an immune response, and providing tumor protection to a subject.

Abstract: Compositions and methods for transport or release of therapeutic and diagnostic agents or metabolites or other analytes from cells, compartments within cells, or through cell layers or barriers are described. The compositions include a membrane barrier transport enhancing agent and are usually administered in combination with an enhancer and/or exposure to stimuli to effect disruption or altered permeability, transport or release. In a preferred embodiment, the compositions include compounds which disrupt endosomal membranes in response to the low pH in the endosomes but which are relatively inactive toward cell membranes (at physiologic pH, but can become active toward cell membranes if the environment is acidified below ca. pH 6.8), coupled directly or indirectly to a therapeutic or diagnostic agent. Other disruptive agents can also be used, responsive to stimuli and/or enhancers other than pH, such as light, electrical stimuli, electromagnetic stimuli, ultrasound, temperature, or combinations thereof.

Abstract: Temperature- and pH-responsive copolymer compositions, and drug delivery devices, conjugates, nanoparticles, and micelles that include the compositions.

Abstract: Conjugates that include polymers that are reversibly self-associative in response to a stimulus and methods for using the conjugates.

Abstract: The invention provides compositions for intracellular delivery of biotinylated cargo. The compositions comprise a complex formed between (a) a fusion protein comprising a protein transduction domain linked to streptavidin and (b) a biotinylated cargo for intracellular delivery. In some embodiments, the protein transduction domain comprises the protein transduction domain of the Human Immunodeficiency Virus type 1 (HIV-1) TAT protein. The complex may further comprise a biotinylated endosomal releasing polymer, such as a poly(propylacrylic acid) polymer. The invention also provides methods for obtaining intracellular delivery of biotinylated cargo and methods for obtaining cytoplasmic delivery of biotinylated cargo.

Abstract: Stimuli-responsive magnetic nanoparticles, methods of making the nanoparticles, and methods of using the nanoparticles.

Abstract: Circularly permuted proteins are described wherein the natural termini of the polypeptide are joined and the resulting circular protein is opened at another point to create new C- and N- termini. The resulting protein exhibits some altered characteristic such as reduced substrate binding, for example. Fusion proteins can be made from the circularly permuted protein by attaching the second polypeptide to these newly created termini. These fusion proteins will have altered properties from a fusion protein made by attaching the second polypeptide to the natural termini. For example, the second peptide or protein can be attached at a position where it is more accessible to its substrate or intended target. In the preferred embodiment, the base circularly permuted biotin binding protein. In one embodiment, a flexible polypeptide loop important for the binding of biotin was opened by creation of the circularly permuted protein. The original termini (residues 13 and 139 of SEQ ID NO:1) were joined by a linker.

Abstract: Streptavidin molecules are disclosed that contain a secondary functional domain. In preferred embodiments, the secondary domain is a cell adhesion peptide incorporated in the streptavidin amino acid sequence at a site not interfering with biotin binding. In a preferred embodiment, the cell adhesion peptide is arginine-glycine-aspartate (Arg-Gly-Asp) (RGD). The peptide is preferably placed on an exposed loop of the streptavidin molecule, such as within the loop defined by residues 63 to 69. The mutant streptavidin molecule can have other characteristics such as reduced biotin binding due to a modification of an amino acid at the biotin binding site. Preferred uses for the disclosed streptavidin molecules are as adaptors to bring, via a streptavidin/biotin interaction, the secondary functional domain into proximity with a cell or molecule to be affected and as a coating for substrates such as vascular devices or prostheses.

Abstract: Streptavidin tetramers have at least one monomer containing an amino acid modification that produces a reduced binding affinity for biotin, a modified off-rate, a modified on-rate, or an altered binding enthalpy. Polynucleotides encoding the modified monomers are also provided. The modified streptavidin and chimeric streptavidin molecules are useful in methods of bioseparations and cell sorting, imaging, drug delivery, and diagnostics.

Abstract: Streptavidin tetramers have at least one monomer containing an amino acid modification that produces a reduced binding affinity for biotin, a modified off-rate, a modified on-rate, or an altered binding enthalpy. Polynucleotides encoding the modified monomers are also provided. The modified streptavidin and chimeric streptavidin molecules are useful in methods of bioseparations and cell sorting, imaging, drug delivery, and diagnostics.

Abstract: The combination of the capabilities of stimuli-responsive components such as polymers and interactive molecules to form site-specific conjugates which are useful in a variety of assays, separations, processing, and other uses is disclosed. The polymer chain conformation and volume can be manipulated through alteration in pH, temperature, light, or other stimuli. The interactive molecules can be biomolecules like proteins or peptides, such as antibodies, receptors, or enzymes, polysaccharides or glycoproteins which specifically bind to ligands, or nucleic acids such as antisense, ribozymes, and aptamers, or ligands for organic or inorganic molecules in the environment or manufacturing processes.