Application of polymersomes engineered to target p32 protein for detection of small breast tumors in mice.

Triple negative breast cancer (TNBC) is the deadliest form of breast cancer and its successful treatment critically depends on early diagnosis and therapy. The multi-compartment protein p32 is overexpressed and present at cell surfaces in a variety of tumors, including TNBC, specifically in the malignant cells and endothelial cells, and in macrophages localized in hypoxic areas of the tumor. Herein we used polyethylene glycol-polycaprolactone polymersomes that were affinity targeted with the p32-binding tumor penetrating peptide LinTT1 (AKRGARSTA) for imaging of TNBC lesions.

Asymmetric Reduction of Prochiral Ketones by Using Self-Sufficient Heterogeneous Biocatalysts Based on NADPH-Dependent Ketoreductases.

The development of cell-free and self-sufficient biocatalytic systems represents an emerging approach to address more complex synthetic schemes under nonphysiological conditions. Herein, we report the development of a self-sufficient heterogeneous biocatalyst for the synthesis of chiral alcohols without the need to add an exogenous cofactor. In this work, an NADPH-dependent ketoreductase was primarily stabilized and further co-immobilized with NADPH to catalyze asymmetric reductions without the addition of an exogenous cofactor.

Efficacy assessment of self-assembled PLGA-PEG-PLGA nanoparticles: Correlation of nano-bio interface interactions, biodistribution, internalization and gene expression studies.

The aim of our study was to develop and compare the biological performance of two types of biodegradable SN-38 loaded nanoparticles (NPs) with various surface properties, composed of low and high Mw triblock PLGA-PEG-PLGA copolymers, applying rational quality and safety by design approach. Therefore, along with the optimization of crucial physico-chemical properties and in order to evaluate the therapeutical potential and biocompatibility of prepared polymeric nanoparticles, analysis of nano-bio interactions, cell internalization, gene expression and biodistribution studies were performed. The optimized formulations, one of low Mw and one composed of high Mw PLGA-PEG-PLGA copolymer, exhibited different characteristics in terms of surface properties, particle size, zeta potential, drug loading, protein adsorption and biodistribution, which may be attributed to the variations in nano-bio interface interactions due to different NP building blocks length and Mw.

Imaging the role of toll-like receptor 4 on cell proliferation and inflammation after cerebral ischemia by positron emission tomography.

The influence of toll-like receptor 4 on neurogenesis and inflammation has been scarcely explored so far by using neuroimaging techniques. For this purpose, we performed magnetic resonance imaging and positron emission tomography with 3'-deoxy-3'-[(18)F]fluorothymidine and [(11)C]PK11195 at 2, 7, and 14 days following cerebral ischemia in TLR4(+/+)and TLR4(-/-)mice. MRI showed similar infarction volumes in both groups.

Synthesis and in vivo evaluation of (11) C-labeled (1,7-dicarba-closo-dodecaboran-1-yl)-N-{[(2S)-1-ethylpyrrolidin-2-yl]methyl}amide.

Boron clusters, and especially dicarba-closo-dodecaboranes, can be used as hydrophobic pharmacophores in the design of new drugs and radiotracers because of their hydrophobic character, spherical structure, and excellent chemical and photochemical stability. In the present paper, the synthesis and in vivo evaluation of (11) C-labeled (1,7-dicarba-closo-dodecaboran-1-yl)-N-{[(2S)-1-ethylpyrrolidin-2-yl]methyl}amide, an analog of the D2 receptor ligand [(11) C]raclopride, is described. The radiosynthesis was approached by reaction of the demethylated precursor with [(11) C]CH3 I in basic media; moderate radiochemical yields (18.

In vivo imaging of dopaminergic neurotransmission after transient focal ischemia in rats.

The precise biologic mechanisms involved in functional recovery processes in response to stroke such as dopaminergic neurotransmission are still largely unknown. For this purpose, we performed in parallel in vivo magnetic resonance imaging and positron emission tomography (PET) with [(18)F]fluorodeoxyglucose ([(18)F]FDG) and [(11)C]raclopride at 1, 3, 7, 14, 21, and 28 days after middle cerebral artery occlusion in rats. In the ischemic territory, PET [(18)F]FDG showed a initial decrease in cerebral metabolism followed by a time-dependent recovery to quasi-normal values at day 14 after ischemia.

Tracing nanoparticles in vivo: a new general synthesis of positron emitting metal oxide nanoparticles by proton beam activation.

The synthesis of (18)F-labelled positron emitting NPs by direct irradiation of (18)O-enriched aluminum oxide NPs with 16 MeV protons is reported. Biodistribution studies of the labelled particles after intravenous administration were performed in male rats using positron emission tomography. The simple and general activation strategy can be applied to any in situ prepared core metal oxide particle for direct use or subsequent bio-compatible coating or encapsulation followed by functionalization.

Biodistribution and metabolism of 11C-labeled Kendine 91 in mice and rats.

The biodistribution pattern of [(11)C]Kendine 91 (a novel HDAC inhibitor) after IV administration has been evaluated using Positron Emission Tomography (rats) and gamma counting of dissected tissues (rats and mice) at different doses (1 μg/kg and 10.0 mg/kg). Metabolism in mice plasma has been also investigated by radio-HPLC.