No abstract

Nanotargeted liposomes may be modified with targeting peptide on the surface of a prepared liposome to endow specificity and elevate targeting efficiency. The aim of this study was to develop a radioactive targeted nanoparticle, the 111In-cyclic RGDfK-liposome, and its advantage of recognizing the αVβ3 integrin was examined. The cyclic RGDfK modified liposomes were demonstrated the ability to bind the αVβ3 integrin expressed on the surface of human melanoma cell in vitro and in vivo. The effects of the cyclic RGDfK-liposome on the functioning of phagocytes was also examined, showing no considerable negative effects on the engulfment of bacteria and the generation of reactive oxygen species. Based upon these findings, the cyclic RGDfK- liposome is said to be a promising agent for tumor imaging.

Elicitation of primary proliferative responses of PBMCs by a protein is generally difficult. We show that Escherichia coli Trx83 with a truncated Trx fold induces PBMC proliferation, but only in the disulfide-reduced form. In contrast, oxidized-form human Trx80 is a potent stimulator. These results demonstrate that the sequence context of an abridged Trx fold is influential in inducing PBMC proliferation. The stimulatory effect of Trx83 is associated with an increase of inflammatory response. The possibility of eliciting PBMC proliferation and switching this activity on/off by redox control provides a perspective for developing Trx83 as a PBMC stimulatory agent. Copyright © 2016 John Wiley & Sons, Ltd.

The pharmacokinetics of N,N-bis(2-mercapatoethly)-N',N'-diethylenediamineRe-BMEDA-liposomes, was studied. In this work, beagles received a single injection of BMEDA, at doses of 1, 2, or 5 mg/kg; the concentration of BMEDA in the beagles' plasma was then analyzed and determined by liquid chromatography-mass spectrometry/mass spectrometry. Based on the pharmacokinetic parameters of BMEDA, we found that male and female animals shared similar patterns indicating that the pharmacokinetics of BMEDA is independent of gender differences. In addition, the pharmacokinetics of BMEDA was seen to be non-linear because the increase of mean AUC 0-t and AUC 0-∞ values tend to be greater than dose proportional while the mean Vss and CL values of BMEDA appeared to be dose dependent. The information on the pharmacokinetics of BMEDA generated from this study will serve as a basis to design appropriate pharmacology and toxicology studies for future human use.

Mutations in leukocyte NADPH oxidase genes lead to defective respiratory burst in white blood cells and cause chronic granulomatous diseases (CGD) in affected patients. The most common form of CGD is caused by mutations in the membrane-bound component of gp91-phox, which is encoded by the CYBB gene located on the X chromosome. We previously reported a patient with CYBB mutation (H338 to Y) which prevents the intracellular trafficking and expression of gp91-phox on the leukocyte surface. By treating the leukocytes with thapsigargin and flavin adenine dinucleotide (FAD), we rescued the capacity of the leukocytes to produce reactive oxygen species (ROS). We visualized the enhanced cell surface expression of the mutant protein after thapsigargin and FAD treatment with GFP-tagged gp91-phox expression with the CGD mutation. Protein and cellular analyses showed that treated cells expressed more endo-H resistant gp91-phox protein and are more effective in killing bacteria. Thapsigargin and FAD-treated CGD leukocytes had enhanced activity in protecting mice from S. aureus-induced peritoneal abscess formation in a mouse model of CGD. These results indicate that thapsigargin and FAD ex vivo treatment is effective in rescuing the ROS-producing activity of leukocytes in selected CGD patients.