Authors:Austin CD, Lawrence DA, Peden AA, Varfolomeev EE, Totpal K, De Mazière AM, Klumperman J, Arnott D, Pham V, Scheller RH, Ashkenazi A
Journal:Proc Natl Acad Sci U S A
PubMed ID:16801533
'Endocytosis is crucial for various aspects of cell homeostasis. Here, we show that proapoptotic death receptors (DRs) trigger selective destruction of the clathrin-dependent endocytosis machinery. DR stimulation induced rapid, caspase-mediated cleavage of key clathrin-pathway components, halting cellular uptake of the classic cargo protein transferrin. DR-proximal initiator caspases cleaved the clathrin ... More
A modular IgG-scFv bispecific antibody topology.
Authors:Orcutt KD, Ackerman ME, Cieslewicz M, Quiroz E, Slusarczyk AL, Frangioni JV, Wittrup KD,
Journal:Protein Eng Des Sel
PubMed ID:20019028
'Here we present a bispecific antibody (bsAb) format in which a disulfide-stabilized scFv is fused to the C-terminus of the light chain of an IgG to create an IgG-scFv bifunctional antibody. When expressed in mammalian cells and purified by one-step protein A chromatography, the bsAb retains parental affinities of each ... More
Self-delivering nanoemulsions for dual fluorine-19 MRI and fluorescence detection.
Authors:Janjic JM, Srinivas M, Kadayakkara DK, Ahrens ET,
Journal:J Am Chem Soc
PubMed ID:18266363
We report the design, synthesis, and biological testing of highly stable, nontoxic perfluoropolyether (PFPE) nanoemulsions for dual 19F MRI-fluorescence detection. A linear PFPE polymer was covalently conjugated to common fluorescent dyes (FITC, Alexa647 and BODIPy-TR), mixed with pluronic F68 and linear polyethyleneimine (PEI), and emulsified by microfluidization. Prepared nanoemulsions (<200 ... More
Development and in vivo efficacy of targeted polymeric inflammation-resolving nanoparticles.
Authors:Kamaly N, Fredman G, Subramanian M, Gadde S, Pesic A, Cheung L, Fayad ZA, Langer R, Tabas I, Farokhzad OC,
Journal:Proc Natl Acad Sci U S A
PubMed ID:23533277
Excessive inflammation and failed resolution of the inflammatory response are underlying components of numerous conditions such as arthritis, cardiovascular disease, and cancer. Hence, therapeutics that dampen inflammation and enhance resolution are of considerable interest. In this study, we demonstrate the proresolving activity of sub-100-nm nanoparticles (NPs) containing the anti-inflammatory peptide ... More
Adsorbed proteins influence the biological activity and molecular targeting of nanomaterials.
The possible combination of specific physicochemical properties operating at unique sites of action within cells and tissues has led to considerable uncertainty surrounding nanomaterial toxic potential. We have investigated the importance of proteins adsorbed onto the surface of two distinct classes of nanomaterials (single-walled carbon nanotubes [SWCNTs]; 10-nm amorphous silica) ... More