A Pyridoindole‐Based Multifunctional Bioprobe: pH‐Induced Fluorescence Switching and Specific Targeting of Lipid Droplets

Abstract

A versatile fluorescent probe, PITE, based on alkyl-substituted pyridoindole (PI) and tetraphenylethylene (TE), which exhibits facile pH-induced fluorescence switching in solution, as nanoparticles, and in the solid state, is presented. Strong fluorescence in the solid state, as well as in solution and the aggregated state, allow sensing of toxic acid vapors. Fluorescence "off-on" switching of PITE through exposure to trifluoroacetic acid and triethylamine vapor is visualized by the naked eye. A unified picture of the switchable fluorescence of PITE is obtained by comprehensive spectroscopic investigations coupled with quantum mechanical calculations. Strong fluorescence, a large Stokes shift, high photostability, and biocompatibility of PITE make it a viable probe for subcellular imaging. Extensive fluorescence microscopic studies by employing organisms including lower and higher eukaryotes reveal specific localization of PITE to lipid droplets (LDs). LDs are dynamic subcellular organelles linked to various physiological processes and human diseases. Hence, the specific detection of LDs in diverse organisms is important to biomedical research and healthcare. Isolation of LDs and subsequent colocalization studies ascertain selective targeting of LDs by the easily affordable, lipophilic bioprobe, PITE. Thus, PITE is a promising multifunctional probe for chemosensing and the selective tracking of LDs.

Recent Advances in Fluorescent Probes for Lipid Droplets

“…PITE [ 28 ] arose from the combination of pyroindole (PI) and tetraphenylethylene (TE) ( Figure 3 ). PI emits strong green fluorescence in organic solvents, while its fluorescence is quenched in aqueous solution due to poor solubility and aggregation.…”

“…The absorption spectra of PITE displays two bands at 320 and 420 nm as contributions of both moieties TE and PI respectively, while it emits at 490 nm and does not depend on excitation wavelength. Using Saccharomyces cerevisiae (as the yeast cell model) and HeLa cells (as the mammalian cell model), Sk et al showed the compatibility of PITE as a blue fluorescent LD probe [ 28 ].…”

Specific Two-Photon Imaging of Live Cellular and Deep-Tissue Lipid Droplets by Lipophilic AIEgens at Ultralow Concentration

“…Great efforts have been made to develop novel lipid droplets dyes to solve these problems. [12][13][14][15][16][17][18][19][20][21] Because the normal concentration used for lipid droplets staining falls in the range of 5-10 μM or even higher, these dyes show weak emission due to the aggregation-caused quenching (ACQ) effect. 22 Few dyes have been synthesized for lipid droplets imaging and function at nano-molar concentrations.…”

Deciphering Molecular Self-Assembly through Electron Microscopy and Fluorescence Correlation Spectroscopy

“…We anticipated that the hydrophobic TPAn might internalize to the lipid-enriched organelles, such as lipid droplets (LDs) through the hydrophobic interactions. 67,68 The spectroscopic features of TPAn inside the living cells were probed through the fluorescence lifetime imaging (FLIM) using a time-resolved confocal microscope. A punctate dot-like pattern in the cytoplasm (ex = 405 nm, em = 435-800 nm), [69][70][71][72] found to be 9 ms (Figure 8a), which is 90 times higher than that in THF.…”