Cysteine-Activatable Near-Infrared Fluorescent Probe for Dual-Channel Tracking Lipid Droplets and Mitochondria in Epilepsy

Abstract

Dual-channel fluorescent probes could respond to a specific target and emit different wavelengths of fluorescence before and after the response. Such probes could alleviate the influence caused by the variation of the probe concentration, excitation intensity, and so on. However, for most dual-channel fluorescent probes, the probe and fluorophore faced spectral overlap, which reduced sensitivity and accuracy. Herein, we introduced a cysteine (Cys)-responsive and near-infrared (NIR) emissive AIEgen (named TSQC) with good biocompatibility to dual-channel monitor Cys in mitochondria and lipid droplets (LDs) during cell apoptosis through wash-free fluorescence bio-imaging. TSQC can label mitochondria with bright fluorescence around 750 nm, and after reacting with Cys, the reaction product TSQ could spontaneously target LDs with emissions around 650 nm. Such spatially separated dual-channel fluorescence responses could significantly improve detection sensitivity and accuracy. Furthermore, the Cystriggered dual-channel fluorescence imaging in LDs and mitochondria during apoptosis induced by UV light exposure, H 2 O 2 , or LPS treatment is clearly observed for the first time. Besides, we also report here that TSQC can be used to image subcellular Cys in different cell lines by measuring the fluorescence intensities of different emission channels. In particular, TSQC shows superior utility for the in vivo imaging of apoptosis in acute and chronic epilepsy mice. In brief, the newly designed NIR AIEgen TSQC can respond to Cys and separate two fluorescence signals to mitochondria and LDs, respectively, to study Cys-related apoptosis.

Polarity-Driven Two-Photon Fluorescent Probe for Monitoring the Perturbation in Lipid Droplet Levels during Mitochondrial Dysfunction and Acute Pancreatitis

“…The reported probes for simultaneously studying LDs and mitochondria can be classified into two categories: (i) polarity driven, − and (ii) exogenous/endogenous-stimuli driven − (Figure b). The cationic form of the probes tends to localize in the mitochondria, whereas the nonionic form localizes in the LD.…”

“…Moreover, depending on the energy requirement, the fatty acids from LDs are oxidized in the mitochondrial matrix via β-oxidation pathway (Figure a). Till now, only a few dual-targeting probes have been employed to study mitochondria and LD, simultaneously. − However, the association of mitochondrial dysfunction with LDs dynamics has not yet been fully established. Indeed, whether it can vary depending on the cell types needs to be also explored.…”

A dual organelle-targeting photosensitizer based on curcumin for enhanced photodynamic therapy

“…[4][5][6] Recently, many organelle-targeting PSs have been developed to improve PDT efficiency because organelles associated with many fundamental life-sustaining activities have become drug targets for disease treatment. [7][8][9] For example, lipid droplets (LDs), which serve as vital organelles for storing neutral lipids in cells, play a crucial role in many physiological processes, such as cell proliferation, migration and activation. 10,11 LDs function as a vital energy source for the proliferation of tumor cells, underscoring the importance of LD-targeted PS research in PDT.…”

A wash-free fluorescent probe with a large Stokes shift for the identification of NAFL through tracing the change of lipid droplets

“…3 In addition to affecting vital activities, such as lipid metabolism and storage and signal transduction, they are also closely related to protein degradation, energy homeostasis, membrane protein expression, membrane transport, and cell migration, differentiation, proliferation and apoptosis. 4,5 As a result, the dysfunction of LDs can give rise to a variety of diseases, including non-alcoholic fatty liver (NAFL), obesity, diabetes, atherosclerosis and many other serious diseases, which have a huge impact on human health. 6 In particular, mounting evidence confirms that the changes in number and size of LDs are closely related to NAFL since the dynamic variation can reflect the metabolic state of liver cells.…”