A Near-Infrared Probe for Specific Imaging of Lipid Droplets in Living Cells

Abstract

Lipid droplets (LDs) are involved in various physiological processes and associated with cancer development, and are regarded as a potential tumor marker for cancer diagnosis. Monitoring LDs is of prior importance to understand their involvement in biological mechanisms and the early detection of cancers. Highly sensitive and specific noninvasive fluorescent probes are particularly desirable for imaging LDs and cancer diagnosis. Herein, according to the high-viscosity and low-polarity microenvironment in LDs, we developed four easily prepared LDsspecific probes based on noncharged merocyanines. Among them, LD-1 absorbs and emits in the near-infrared (NIR) region with a large Stokes shift. Importantly, LD-1 displayed high sensitivity to high viscosity and low polarity, which allowed it to show high LDstargeting ability. In cell imaging, LD-1 successfully probed the changes in LDs in the presence of oleic acid or during ferroptosis and was used to distinguish cancer cells from normal cells.

Highly Efficient Red/NIR-Emissive Fluorescent Probe with Polarity-Sensitive Character for Visualizing Cellular Lipid Droplets and Determining Their Polarity

“…As shown in Table , the fluorescence wavelengths of probe LDs-Red in cancer cells (maxima of 611.9–615.4 nm) are certainly shorter than those in normal cells (maxima of 623.3–626.0 nm). Recently, there are also several literature studies which report the polarity-sensitive LD fluorescent probes for distinguishing cancer cells from normal cells. − However, they are generally based on the difference in fluorescence intensity between cancer and normal cells. As well known, the fluorescence intensity of imaging would be easily disturbed by many factors, such as the fluorescent probe concentration, the excitation laser intensity, the exposing time of each pixel, the fluorescence detection efficiency, and so on.…”

“…Garcia-Fernandez, Orte, and co-workers reported an idea of acridone excimers for fluorescence lifetime imaging to determine the LD polarity . Moreover, several polarity-sensitive LD fluorescent probes were proposed to be able to distinguish cancer cells from normal cells, − such as CTPA developed by Lin’ group, LD-TTP reported by Dong and co-workers, and LD-1 synthesized by Tang’s group . These fluorescent probes would display significantly stronger fluorescence in cancer cells than in normal cells because the LDs in cancer cells generally have lower polarity and larger number than in normal cells.…”

“…32 Moreover, several polarity-sensitive LD fluorescent probes were proposed to be able to distinguish cancer cells from normal cells, 36−45 such as CTPA developed by Lin' group, 36 LD-TTP reported by Dong and co-workers, 37 and LD-1 synthesized by Tang's group. 38 These fluorescent probes would display significantly stronger fluorescence in cancer cells than in normal cells because the LDs in cancer cells generally have lower polarity and larger number than in normal cells. These reports highlight the powerful utility of polarity-sensitive LD fluorescent probes and give significant contributions to the biological study.…”

Recent advances in small-molecule fluorescent probes for studying ferroptosis

“…20). 155 These probes featured the merocyanine scaffold bearing diethylamino or methoxy moiety directly linked to the aurone group modified with or without hydroxyl group, which constructed a classic D–π–A platform for polarity detection. In the meantime, the aurone and diethylamino parts were also expected to serve as molecular rotors which enabled the probes to track viscosity.…”

A lipid droplet-specific fluorescence probe for atherosclerotic plaque imaging

“…In recent years, fluorescence imaging has emerged as one of the most popular techniques for LD imaging with high performance, real-time visibility, great sensitivity and high resolution. [20][21][22][23][24] Therefore, various fluorescent dyes have been utilized for LD imaging, [25][26][27][28][29] the most common of which are Nile red and BODIPY 493/503. [30][31][32][33] However, Nile red suffers from low specificity and a wide range of emission, resulting in a low signal to noise ratio (SNR) and low applicability in multicolor imaging.…”