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

Abstract

Lipid droplets are highly associated with obesity, diabetes, inflammatory disorders and cancer. A reliable two-photon dye for specific lipid droplets imaging in live cells and live tissues at ultra-low concentration has rarely been reported. In this work, four new aggregation-induced emission luminogens (AIEgens) based on the naphthalene core were designed and synthesized for specific two-photon lipid droplets staining. The new molecules, namely NAP AIEgens, exhibit large Stokes shift (>110 nm), high solid-state fluorescence quantum yield (up to 30%), good two-photon absorption cross section (45-100 GM at 860 nm), high biocompatibility and good photostability. They could specifically stain lipid droplets at ultra-low concentration (50 nM) in a short time of 15 min. Such ultra-low concentration is the lowest value for lipid droplets staining in live cells reported so far. In vitro and ex vivo two-photon imaging of lipid droplets in live cells and live mice liver tissues were successfully demonstrated. In addition, selective visualization of lipid droplets in live mice liver tissues could be achieved at a depth of about 70 μm. These excellent properties render them as promising candidates for investigating lipid droplets-associated physiological and pathological processes in live biological samples.

Enzyme‐Mediated Tumor Starvation and Phototherapy Enhance Mild‐Temperature Photothermal Therapy

“…According to the references, [ 16 ] A549 cells were seeded in 96‐well plates at a density of 5 × 10 3 per well. The cells were incubated with ILs, IGLs, GOILs, or GOIGLs at different ICG concentrations, followed with/without 10 min white light irradiation at 10 mW cm −2 and/or 10 min 808 nm NIR laser irradiation at 0.3 W cm −2 .…”

Visualization of intracellular lipid droplets using lipophilic benzothiazole-based push-pull fluorophores at ultralow concentration

“…Heretofore, few probes for the tracking of lipid droplets at ultralow concentration (≤ 100 nM) have been reported in 9 the literature. [17] In addition, this report is, to date, the lowest reported concentration to stain LDs in cells using solvatofluorochromic fluorophores. [24][25][26][27] This value is significantly above the lower threshold value (ClogP = 5) usually required for lipid droplet staining, as estimated by…”

“…To overcome such drawbacks and enhance the staining stability and selectivity for lipid droplets, the quest for new fluorogenic probes with superior photophysics and different operation modes was undertaken. [16] Prospective advances in molecular platforms for LDs staining have been recently published, exploiting numerous hydrophobic fluorogenic probes including AIEgens (aggregation induced emission luminogens), [17][18][19][20][21][22] solvatochromic StatoMerocyanine dyes, [23] and solvatofluorochromic fluorophores displaying emission from intramolecular charge transfer excited states. [24][25][26][27] In our laboratory, we have recently developed a new set of environment responsive D-π-A fluorophores and demonstrated their high biocompatibility, fine-tuned spectroscopic properties, and their smooth chemical transformation into molecular probes for biological applications.…”

Hydrazide–Hydrazone Small Molecules as AIEgens: Illuminating Mitochondria in Cancer Cells

“…[7][8][9][10] To introduce biocompatibility for imaging and therapy,t he majority of the AIEgensw as tagged with hydrophilic moieties to decorate hydrophobic AIE core through multiple synthetic steps. [16][17][18][19][20][21] The mitochondrion is one of the most important organelles whicho rchestrate several cellular functions, hence implicated in different diseased states including cancer. [16][17][18][19][20][21] The mitochondrion is one of the most important organelles whicho rchestrate several cellular functions, hence implicated in different diseased states including cancer.…”

“…[11][12][13][14][15] Recently,n umerous biocompatible AIEgensh ave been developed for in vitro cellular imaging, especially to visualize intracellular organelles. [16][17][18][19][20][21] The mitochondrion is one of the most important organelles whicho rchestrate several cellular functions, hence implicated in different diseased states including cancer. [22][23][24] As ar esult, visualizing mitochondria inside cancer cells is of utmost importance to understand their form and function in cancerp rogression and management.A lthough several TPE-and HPS-based AIEgens have been explored lately, [25][26][27][28][29][30] there is still as eriousl ack of biocompatible small-molecule AIEgensf or visualization of mitochondria in cancer cells.…”