Proteinosomes are a type of protein-based spherical capsules, which have potential applications in drug delivery, cell imaging, gene expression, and biocatalysis. In this research, a novel approach to the fabrication of proteinosomes entirely composed of protein molecules based on self-assembly of a supramolecular protein-polymer conjugate is proposed. A supramolecular protein-polymer conjugate was prepared by mixing βCD-modified bovine serum albumin (BSA) and adamantane-terminated poly(N-isopropylamide) (Ad-PNIPAM) in aqueous solution. The BSA-PNIPAM bioconjugate self-assembled into micelles with PNIPAM cores and BSA coronae at a temperature above the lower critical solution temperature (LCST) of PNIPAM. After cross-linking of BSA in the coronae, and followed by addition of excess βCD, PNIPAM chains were cleaved from the micellar structures, and nanoscale proteinosomes were prepared. The dual-responsive proteinosomes dissociated in the presence of trypsin or glutathione.
Combinations of synthetic polymers and natural proteins provide a route to the synthesis of new biomaterials. The bioconjugates combining tunable properties of polymers with functionalities of proteins have found broad applications. One of the most challenging problems in this research field is the self-assembly behaviors of responsive polymer−protein bioconjugates. In this research, synthesis and self-assembly of bioconjugates composed of zwitterionic block copolymer and streptavidin were investigated. Block copolymers of poly(ethylene glycol) (PEG) and poly[3-dimethyl(methacryloyloxyethyl)ammonium propanesulfonate] (PDMAPS) with cleavable biotin groups at the junction points were synthesized. The zwitterionic block copolymers exhibit phase transitions with upper critical solution temperatures (UCSTs) in aqueous solutions. The concentration of sodium chloride exerts a significant influence on the UCST. The zwitterionic block copolymer chains selfassemble into vesicles in aqueous solution at a temperature below UCST. Bioconjugates comprising of streptavidin molecules and zwitterionic block copolymer chains were fabricated based on biotin−streptavidin coupling. Upon conjugation to the protein molecules, the UCST of the zwitterionic block copolymer decreases due to the screening effect of the protein molecules. The bioconjugates are able to make self-assembly into different structures, depending on the average number of block copolymer chains on a protein molecule. The bioconjugate molecules with average 1.3 block copolymer chains on a streptavidin selfassemble into rodlike structures, while those with average 2.9 chains on a streptavidin self-assemble into spherical micelles.
Natural products are a major source for cancer drug development. NK cells are a critical component of innate immunity with the capacity to destroy cancer cells, cancer initiating cells, and clear viral infections. However, few reports describe a natural product that selectively stimulates NK cell IFN-γ production and unravel a mechanism of action. In this study, through screening, we found that a natural product, phyllanthusmin C (PL-C), alone enhanced IFN-γ production by human NK cells. PL-C also synergized with IL-12, even at the low cytokine concentration of 0.1 mg/ml, and stimulated IFN-γ production in both human CD56bright and CD56dim NK cell subsets. Mechanistically, TLR1 and/or TLR6 mediated PL-C’s activation of the NF-κB p65 subunit that in turn bound to the proximal promoter of IFNG and subsequently resulted in increased IFN-γ production in NK cells. However, IL-12/IL-15 receptors and their related STAT signaling pathways were not significantly modulated by PL-C. PL-C induced little or no T cell IFN-γ production or NK cell cytotoxicity. Collectively, we identify a natural product with the capacity to selectively activate human NK cell IFN-γ. Given the role of IFN-γ in immune surveillance, additional studies to understand the role of this natural product in prevention of cancer or infection in select populations are warranted.
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