Antibody-targeting of ultra-small nanoparticles enhances imaging sensitivity and enables longitudinal tracking of multiple myeloma

Monitoring malignant progression and disease recurrence post-therapy are central challenges to improving the outcomes of patients with multiple myeloma (MM). Whereas current detection methods that rely upon bone marrow examination allow for precise monitoring of minimal residual disease and can help to elucidate clonal evolution, they do not take into account the spatial heterogeneity of the tumor microenvironment. As such, they are uninformative as to the localization of malignant plasma cells and may lead to false negative results. With respect to the latter challenge, clinically-available imaging agents are neither sufficiently sensitive nor specific enough to detect minute plasma cell populations. Here, we sought to explore methods by which to improve detection of MM cells within their natural bone marrow environment, using whole-animal magnetic resonance imaging to longitudinally monitor early-stage disease as well as to enhance tumor detection after systemic therapy. We conducted a proof-of-concept study to demonstrate that ultra-small

Inhibition of the Mitochondrial Enzyme ABAD Restores the Amyloid-β-Mediated Deregulation of Estradiol

Alzheimer's disease (AD) is a conformational disease that is characterized by amyloid-β (Aβ) deposition in the brain. Aβ exerts its toxicity in part by receptor-mediated interactions that cause down-stream protein misfolding and aggregation, as well as mitochondrial dysfunction. Recent reports indicate that Aβ may also interact directly with intracellular proteins such as the mitochondrial enzyme ABAD (Aβ binding alcohol dehydrogenase) in executing its toxic effects. Mitochondrial dysfunction occurs early in AD, and Aβ's toxicity is in part mediated by inhibition of ABAD as shown previously with an ABAD decoy peptide. Here, we employed AG18051, a novel small ABAD-specific compound inhibitor, to investigate the role of ABAD in Aβ toxicity. Using SH-SY5Y neuroblastoma cells, we found that AG18051 partially blocked the Aβ-ABAD interaction in a pull-down assay while it also prevented the Aβ42-induced down-regulation of ABAD activity, as measured by levels of estradiol, a known hormone and product of ABAD activity. Furthermore, AG18051 is protective against Aβ42 toxicity, as measured by LDH release and MTT absorbance. Specifically, AG18051 reduced Aβ42-induced impairment of mitochondrial respiration and oxidative stress as shown by reduced ROS (reactive oxygen species) levels. Guided by our previous finding of shared aspects of the toxicity of Aβ and human amylin (HA), with the latter forming aggregates in Type 2 diabetes mellitus (T2DM) pancreas, we determined whether AG18051 would also confer protection from HA toxicity. We found that the inhibitor conferred only partial protection from HA toxicity indicating distinct pathomechanisms of the two amyloidogenic agents. Taken together, our results present the inhibition of ABAD by compounds such as AG18051 as a promising therapeutic strategy for the prevention and treatment of AD, and suggest levels of estradiol as a suitable read-out

Thermal bistability-based method for real-time optimization of ultralow-threshold whispering gallery mode microlasers

International audienceA method based on thermal bistability for ultralow-threshold microlaser optimization is demonstrated. When sweeping the pump laser frequency across a pump resonance, the dynamic thermal bistability slows down the power variation. The resulting line shape modification enables a real-time monitoring of the laser characteristic. We demonstrate this method for a functionalized microsphere exhibiting a submicrowatt laser threshold. This approach is confirmed by comparing the results with a step-by-step recording in quasi-static thermal conditions

Thermal bistability-based method for real-time optimization of ultralow-threshold whispering gallery mode microlasers

Region Ile-de-France; China Scholarship CouncilA method based on thermal bistability for ultralow-threshold microlaser optimization is demonstrated. When sweeping the pump laser frequency across a pump resonance, the dynamic thermal bistability slows down the power variation. The resulting line shape modification enables a real-time monitoring of the laser characteristic. We demonstrate this method for a functionalized microsphere exhibiting a submicrowatt laser threshold. This approach is confirmed by comparing the results with a step-by-step recording in quasi-static thermal conditions. (C) 2012 Optical Society of Americ

Delocalization of 4f electrons in gadolinium oxide on the nanometer scale

cited By 5International audienc

Delocalization of 4f electrons in gadolinium oxide on the nanometer scale

cited By 5International audienc

Gd-nanoparticles functionalization with specific peptides for ß-amyloid plaques targeting.

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