Near-infrared fluorescent sensor for in vivo copper imaging in a murine Wilson disease model

Abstract

Copper is an essential metal nutrient that is tightly regulated in the body because loss of its homeostasis is connected to severe diseases such as Menkes and Wilson diseases, Alzheimer’s disease, prion disorders, and amyotrophic lateral sclerosis. The complex relationships between copper status and various stages of health and disease remain challenging to elucidate, in part due to a lack of methods for monitoring dynamic changes in copper pools in whole living organisms. Here we present the synthesis, spectroscopy, and in vivo imaging applications of Coppersensor 790, a first-generation fluorescent sensor for visualizing labile copper pools in living animals. Coppersensor 790 combines a near-infrared emitting cyanine dye with a sulfur-rich receptor to provide a selective and sensitive turn-on response to copper. This probe is capable of monitoring fluctuations in exchangeable copper stores in living cells and mice under basal conditions, as well as in situations of copper overload or deficiency. Moreover, we demonstrate the utility of this unique chemical tool to detect aberrant increases in labile copper levels in a murine model of Wilson disease, a genetic disorder that is characterized by accumulation of excess copper. The ability to monitor real-time copper fluxes in living animals offers potentially rich opportunities to examine copper physiology in health and disease.

In vivo bioluminescence imaging reveals copper deficiency in a murine model of nonalcoholic fatty liver disease

“…However, the vast majority of these tools have been limited to dissociated cell culture and related thin specimens (e.g., zebrafish), and current examples of in vivo copper imaging in mammalian models remain rare owing to the challenges of coupling a selective and sensitive response to copper with modalities that offer tissue penetration at appropriate depths (16,(34)(35)(36)(37)(38)(39). Moreover, none of these technologies allow for in vivo copper imaging in a targeted cell-or tissue-specific manner.…”

In Vivo Metal Ion Imaging Using Fluorescent Sensors

“…Our own contribution, CS790AM, is an NIR fl uorescent Cu + sensor (Fig. 1b ) that was used to detect Cu + fl uctuations in living mice, including a murine model of Wilson's disease [ 15 ].…”

Alleviation of photosynthetic inhibition in copper-stressed tomatoes through rebalance of ion content by exogenous nitric oxide

“…Insufficient supply of Cu can result in abnormal plant growth and development, both of which have been widely reported in previous studies (Yu and Rengel, 1999;Andrés-Colás et al, 2013). However, an excess of Cu, a serious environmental problem arising and spreading together with industrialization and the improper management of fertilizers and irrigation in agriculture in the past decades, can also adversely affect physiological processes and biochemical reactions in organisms and endanger the environment and, more particularly, human health (Hirayama et al, 2012;Wen et al, 2013). Therefore, increasing knowledge about how plants respond to Cu stress can greatly contribute to applied technologies, such as metal phytoextraction, to improve crop yield and quality in contaminated soil and to protect environmental safety (Seth et al, 2011).…”