WO2017080449A1 - Luminogènes aie fluorescents rouges - Google Patents

Luminogènes aie fluorescents rouges Download PDF

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WO2017080449A1
WO2017080449A1 PCT/CN2016/105157 CN2016105157W WO2017080449A1 WO 2017080449 A1 WO2017080449 A1 WO 2017080449A1 CN 2016105157 W CN2016105157 W CN 2016105157W WO 2017080449 A1 WO2017080449 A1 WO 2017080449A1
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aiegen
ascp
aiegens
acceptor
group
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PCT/CN2016/105157
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Benzhong Tang
Yee Yung Yu
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The Hong Kong University Of Science And Technology
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    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
    • C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0071—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by measuring fluorescence emission
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/645—Specially adapted constructive features of fluorimeters
    • G01N21/6456—Spatial resolved fluorescence measurements; Imaging
    • G01N21/6458—Fluorescence microscopy
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
    • G01N2021/6439—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" with indicators, stains, dyes, tags, labels, marks

Definitions

  • the present subject matter relates to the synthesis and application of red fluorescent AIEgens.
  • the present subject matter relates to mitochondrial targeting AIEgens, which boost the radiosensitivity of lung carcinoma.
  • the present AIEgens can also target cell membranes, lipid droplets, or lysosomes, as well as serve as a radio sensitizer in radiotherapy.
  • the present subject matter further relates to two-photon imaging with AIEgens.
  • Fluorescent dyes have been used widely in modern biological studies and have facilitated the development of fluorescent microscopes. Fluorescent imaging is a powerful tool to look beyond tissue and observe single cells and, nowadays, has an important role in the progression and noninvasive study of gene expression, protein function, protein-protein interactions, and many other cellular processes.
  • fluorescent imaging has proved to be a powerful tool in examining the microscopic structures of polymer blends.
  • FR/NIR near-infrared
  • fluorescent imaging allows for obtaining insight not only of the surface pattern, but also of deeper layers.
  • the aggregation-caused quenching (ACQ) effect has always given rise to photo-bleaching and attenuation in fluorescence intensity upon aggregation, thus resulting in restrictions of long-time monitoring of organelles and lower performance.
  • AIE active molecules are highly emissive in aggregated and/or crystalline states due to restriction of intra-molecular motions (RIM) , allowing applications in various areas, such as in OLEDs and bioprobes.
  • RIM intra-molecular motions
  • AIE active molecules have already been applied successfully as bioprobes, proving to possess high photostability and high bio-compatibility.
  • the present subject matter is directed to a method for preparing red fluorescent AIEgens for biological applications having aggregation induced emission characteristics comprising combining a donor selected from the group consisting of tertiary amino, alkoxy, and imidazole groups and an acceptor selected from the group consisting of cyano, pyridium, and indolium.
  • the present subject matter is directed to a method of preparing AIEgens, comprising constructing a donor-acceptor AIE derivative compound, wherein the donor-acceptor AIE derivative comprises a backbone structure of a formula selected from the group consisting of:
  • R, R’ , R” , and R” ’ are independently selected from the group consisting of:
  • n is an integer from 0 to 20.
  • the present subject matter is directed to an AIEgen for use as a dye comprising a donor-acceptor AIE derivative compound, wherein the donor-acceptor AIE derivative comprises a backbone structure of a formula selected from the group consisting of:
  • R, R’ , R” , and R” ’ are independently selected from the group consisting of:
  • n is an integer from 0 to 20.
  • the present subject matter is directed to an AIEgen having a structure of:
  • the present subject matter is directed to an AIEgen having a structure of:
  • FIG. 2 shows (A) PL spectra of ASCP in toluene/DMSO mixtures with different toluene fractions (f t ) .
  • FIG. 3 shows viability of HeLa cells in the presence of different concentrations of ASCP for 8 h. Data is expressed as mean value for five separate trials.
  • FIG. 4 shows (Aand B) fluorescent and (C) bright-field images of HeLa cells stained with ASCP (5 ⁇ M) for 30 min with focus at mitochondria (A) and nucleolus (B) , respectively.
  • D and E Confocal images of HeLa cells stained with (D) ASCP (5 ⁇ M) and (E) MitoTracker green (MTG; 200 nM) .
  • FIG. 7 shows fluorescent images of HeLa cells stained with (A-C) ASCP (10 ⁇ M) for 2 h and (D-F) SYTO RNASelect (5 ⁇ M) for 2 h with or without treatment with RNase or DNase.
  • FIG. 8 shows confocal images of HeLa cells stained with (A and C) ASCP and (B and D) SYTO RNASelect taken under continuous excitation.
  • FIG. 9 shows absorption spectra of ASCP-2P in DMSO solution.
  • FIG. 10 shows (A) PL spectra of ASCP-2P in toluene/DMSO mixtures with different toluene fractions (f t ) and (B) plot of relative emission intensity (I/I 0 ) at 640 nm versus the composition of the toluene/DMSO mixture of ASCP-2P.
  • FIG. 12 shows (A) PL spectra of H2DCFDA (5 ⁇ M) with ASCP-2P (10 ⁇ M) in PBS solutions under different irradiation of white light and (B) change in fluorescent intensity at 534 nm of PBS solutions containing different AIEgens (10 ⁇ M) and H2DCFDA (5 ⁇ M) with different irradiation time of white light.
  • ⁇ ex 495 nm.
  • FIG. 14 shows (A and B) confocal images and (C) merged image with bright-field of A549 cancer cells co-stained with ASCP-2P (5 ⁇ M) and MitoTracker Deep Red (MTDR, 50 nM) .
  • Confocal images show the intracellular ROS levels of A549 cancer cells received different treatments by using H2DCFDA as the ROS indicator.
  • D Probe +, Light -
  • E Probe +, Light +
  • F Probe +, Light +, NAC+.
  • FIG. 15 shows cell viability of A549 cells incubated with ASCP-2P in dark (Black) , ASCP-2P pretreated with white light irradiation for 1 min and followed by in dark (Red) and ASCP-2P with NAC pretreated with white light irradiation for 1 min and followed by in dark (Blue) .
  • FIG. 16 shows (A) clonogenic formation upon different treatments and (B) quantitative data for clonogenic assay of (A) . **represents P ⁇ 0.01.
  • FIG. 17 shows (A) clonogenic formation after treatment with different popularly used radiosensitizer and (B) quantitative data for clonogenic assay of (A) . **represents P ⁇ 0.01.
  • FIG. 18 shows Western blot analysis of (A) p-ERK, ERK, p-Akt and Akt; (B) Bcl-XL, Bcl-2, BAD, and Caspase-3; and (D) p-ERK, p-Akt, Bcl-2, Bax and BAD from A549 cells with various treatments indicated.
  • (C) shows an illustration of the pathway that indicates how ASCP-2P serves as an effective radiosensitizer to irradiation.
  • FIG. 19 shows absorption spectra of 3” in THF solution.
  • FIG. 20 shows absorption spectra of 5” in THF solution.
  • FIG. 21 shows (A) PL spectra of 3” in THF/water mixture with different water fractions (f w ) and (B) plot of relative PL intensities versus f w .
  • I 0 are the PL intensities at 580 nm of the dyes in THF; Dye concentration: 10 ⁇ M; excitation wavelength: 410 nm.
  • FIG. 22 shows (A) PL spectra of 5” in THF/water mixture with different water fractions (f w ) and (B) plot of relative PL intensities versus f w .
  • I 0 are the PL intensities at 680 nm of the dyes in THF; Dye concentration: 10 ⁇ M; excitation wavelength: 525 nm.
  • FIG. 23 shows fluorescent images of HeLa cells co-stained with 3” (5 ⁇ M) and Lyso-tracker red for 15 min.
  • Lyso-tracker red Ex. : 520-560 nm
  • B 16: Ex. : 400-440 nm
  • C and D merge imaging without daylight and image of daylight.
  • FIG. 24 shows confocal images of HeLa cell stained with 3” (5 ⁇ M) for 15 min and excited by 442 nm and 840 nm. Em: 500-580 nm.
  • FIG. 25 shows confocal images of HeLa cell stained with 5” (5 ⁇ M) for 30 min and excited by 512 nm and 1000 nm.
  • Em 520-630 nm.
  • FIG. 26 shows PL spectra in confocal images ⁇ : PL signals in lipid droplets; ⁇ : PL signals outside lipid droplets.
  • Aggregation-induced emission means the fluorescence/phosphorescence is turned on upon aggregation formation or in the solid state. When molecularly dissolved, the material is nonemissive. However, the emission is turned on when the intramolecular rotation is restricted.
  • Emission intensity means the magnitude of fluorescence/phosphorescence normally obtained from a fluorescence spectrometer or fluorescence microscopy measurement.
  • Fluorophore means a molecule which exhibits fluorescence.
  • Luminogen means a molecule which exhibits luminescence.
  • AIEgen means a molecule exhibiting AIE characteristics.
  • the present subject matter is directed to different approaches used to prepare red fluorescent AIEgens.
  • one possible approach is based on the designed donor-acceptor structure.
  • red-emitting AIEgens are designed and their biological applications are demonstrated by selective staining of polymers in blends.
  • cyano-substituted stilbene derivatives different donors are incorporated into the molecular backbone and donor-acceptor systems are formed, leading to a tunable emission from yellow to red.
  • targeting moieties are attached to these molecules for organelle-specific imaging. Their biological applications are also explored, including mitochondria-specific imaging and radiotherapy.
  • the present subject matter is directed to a method for preparing red fluorescent AIEgens for biological applications having aggregation induced emission characteristics comprising combining a donor selected from the group consisting of tertiary amino, alkoxy, and imidazole groups and an acceptor selected from the group consisting of cyano, pyridium, and indolium.
  • a donor selected from the group consisting of tertiary amino, alkoxy, and imidazole groups
  • an acceptor selected from the group consisting of cyano, pyridium, and indolium.
  • the present compounds sometimes referred to as donor-acceptor compounds, have a donor-acceptor structure in one embodiment herein.
  • the fluorescent signals of the AIEgens of the present subject matter are around 600 nm.
  • the present subject matter is directed to method of preparing AIEgens, comprising constructing a donor-acceptor AIE derivative compound, wherein a donor-acceptor AIE derivative comprises a backbone structure of a formula selected from the group consisting of:
  • R, R’ , R” , and R” ’ are independently selected from the group consisting of:
  • n is an integer from 0 to 20.
  • the AIEgen of the present subject matter exhibits red fluorescence.
  • the AIEgen of the present subject matter is used for fluorescent cell imaging of lung carcinoma cells.
  • the donor-acceptor AIE derivatives of the present subject matter can target specific organelles selected from the group consisting of mitochondria, nucleolus, lysosomes, cell membranes, and lipid droplets.
  • the present subject matter is directed to an AIEgen for use as a dye comprising a donor-acceptor AIE derivative, wherein a donor-acceptor AIE derivative comprises a backbone structure of a formula selected from the group consisting of:
  • R, R’ , R” , and R” ’ are independently selected from the group consisting of:
  • n is an integer from 0 to 20.
  • the AIEgen of the present subject matter has a structure of:
  • the AIEgen of the present subject matter is a dye for targeting mitochondria and nucleolus.
  • the AIEgen of the present subject matter has a structure of:
  • the AIEgen of the present subject matter is a dye for targeting mitochondria.
  • the AIEgen of the present subject matter can be a radio sensitizer in radiotherapy.
  • the present subject matter is directed to an AIEgen having a structure of:
  • the AIEgen of the present subject matter is a dye for targeting lysosomes.
  • the AIEgen of the present subject matter can be used for two-photon imaging.
  • the present subject matter is directed to an AIEgen having a structure of:
  • the AIEgen of the present subject matter is a dye for targeting lipid droplets.
  • the AIEgen of the present subject matter can be used for two-photon imaging.
  • the specific AIEgen ASCP is a dual-color organelle-specific probe with AIE features for targeting the mitochondria and nucleolus. Due to different interactions with the mitochondrial membrane and nucleic acids, distinct emission colors from the mitochondria and nucleolus are observed under fluorescence microscopy. Owing to high brightness, excellent biocompatibility, and superior photostability, the AIE fluorescent probe ASCP is a promising candidate for simultaneous mitochondria and nucleolus imaging.
  • ASCP optical properties were studied. Due to the hydrophilic nature of the Py salt, ASCP is soluble in polar solvents, slightly soluble in water, but insoluble in nonpolar solvents such as dioxane and toluene. ASCP exhibits an absorption band at around 450 nm, irrespective of the type of solvent used (FIG. 1A) . On the contrary, it shows obvious different emission colors and intensities when the measurement was carried out in different solvents (FIG. 1B) .
  • ASCP emits a strong orange light in dilute dioxane solution. Owing to the twisted intramolecular charge transfer (TICT) effect, the emission of the dye molecule was weakened and red-shifted by increasing the solvent polarity. In dilute DMSO solution, ASCP shows a faint red fluorescence. In contrast, gradual addition of toluene into its DMSO solution has enhanced the light emission and changed the emission color to orange due to the gradual decrement of the solvent polarity (FIG. 2) . At a high toluene fraction, a much more rapid fluorescence enhancement was observed, which was due to the formation of ASCP aggregates along with the activation of the AIE process.
  • TCT twisted intramolecular charge transfer
  • the strong emission of ASCP in the aggregated state encourages utilization as a fluorescent visualizer for mitochondrion imaging.
  • the cytotoxicity of ASCP on HeLa cells was first evaluated using MTT assay. As depicted in FIG. 3, the cell viability remains high at ASCP concentrations as high as 10 ⁇ M, suggesting that ASCP possesses a good biocompatibility.
  • ASCP was first assessed for its capability to stain specific organelles in live HeLa cells.
  • the HeLa cells were cultured and incubated in MEM with 5 ⁇ M ASCP for 30 min.
  • the cells were washed with fresh PBS and then observed under fluorescence microscope. Thanks to the high specificity of the Py unit in ASCP, the reticulum structures of mitochondria are stained with an intense orange emission (FIG. 4A) .
  • MitoTracker Green (MTG) , a commercial mitochondrial imaging agent, was used to co-stain the HeLa cells.
  • MTG MitoTracker Green
  • the cell images taken on confocal microscopy illustrate that the orange fluorescence from ASCP has an excellent correlation (96.4%) with the green emission of MTG (FIG. 4D-F) .
  • phospholipids and nucleic acids The most abundant components in the mitochondria and nucleolus are phospholipids and nucleic acids (DNAs and RNAs) , respectively.
  • DNAs and RNAs phospholipids found in the mitochondrial membrane and nucleic acids were chosen for mimicking the actual intracellular environment.
  • Different lipid vesicles were first fabricated as models of mitochondria by mixing desired ratio of phospholipids.
  • the absorption and emission spectra of ASCP in the presence of lipid vesicles and nucleic acids in HEPES were then recorded.
  • ASCP exhibits an absorption maximum at 435 nm in HEPES, showing no or little wavelength shift when treated with lipid vesicles.
  • ASCP may be used to collect individual fluorescence from mitochondria and nucleolus without cross contamination. Confocal images of dye-labelled HeLa cells were collected by changing the excitation wavelengths and the emission filters. After optimizing the conditions, mitochondria can be visualized individually with orange fluorescence under 405 nm light excitation (FIG. 6A) . On the other hand, only red fluorescence was observed in nucleoli at an excitation wavelength of 560 nm (FIG. 6B) .
  • ASCP Intercalation and electrostatic attraction are possible interactions between ASCP and nucleic acids.
  • ASCP enters the cavities of nucleic acids, it may adopt a more co-planar and conjugated conformation, and hence shows a redder emission.
  • the hydrogen bonds between the nucleotides in nucleic acids may provide a relative polar environment for ASCP to emit at the longer wavelength region.
  • SYTO RNASelect a commercial fluorescent probe for the nucleolus.
  • SYTO RNASelect performed similar to ASCP. Since RNA contributes the major constituent in the nucleolus, both ASCP and SYTO RNASelect tend to accumulate in the nucleolus due to the strong electrostatic attraction. When the dye-labelled cells are treated with RNase, the binding sites for intercalation are collapsed, and the dye molecules no longer bind to the RNA fragments. Thus, the fluorescent emission of ASCP and SYTO RNASelect in RNA-rich nucleolus is decreased dramatically.
  • ASCP-2P is a red-emissive AIEgen, designed and synthesized with a strong donor-acceptor structure.
  • ASCP-2P is AIE-active and mitochondrial targeting, and its ROS generation ability was studied and verified by a commercial ROS sensor.
  • ASCP-2P was utilized as a photosensitizer to increase the radiosensitivity of lung carcinoma cells in radiotherapy, obtaining an ultra-high value of SER10 compared with paclitaxel and gold nanoparticles. Apoptotic death path was identified by Western blot analysis. The first demonstration of the photosensitizer in radiotherapy showed high potential for cancer treatment.
  • the photophysical properties of ASCP-2P were studied.
  • the maximum absorption of ASCP-2P was at 460 nm (FIG. 9) .
  • the fluorescent property was studied in mixtures of DMSO and toluene. There was nearly no emission in pure DMSO solution. Upon addition of toluene to the DMSO solution, the fluorescent intensities gradually increased and blue-shifted from 660 nm to 620 nm, but there were further dramatic enhancements after 80%toluene fraction (FIG. 10) .
  • ASCP-2P structure is a strong donor-acceptor design similar to ASCP, a strong TICT property was revealed.
  • ASCP-2P was molecularly dissolved in DMSO solution, and the emission was weaken by the TICT effect and discouraged by the free intramolecular motions through non-radiative decay. Toluene served as a poor solvent to induce aggregate formation of ASCP-2P.
  • the slight enhancement and a blue shift was due to the TICT effect because of the low polarity of toluene.
  • the significant enhancement was due to aggregate formation, activating the RIM process and relaxing in the radiative channel.
  • ASCP-2P reveals AIE characteristics, but also TICT effects from the strong donor-acceptor structure.
  • Py group has been reported to be a mitochondria targeting group.
  • the mitochondrial membrane environment was mimicked by preparing a lipid vesicle and mixing with ASCP-2P in PBS solution (FIG. 11) .
  • the weak emission in PBS solution was due to the TICT effect in a highly polar aqueous solution. After binding to phospholipids, the motions of ASCP-2P were restricted, activating the RIM process and blocking non-radiative decay.
  • AIEgens have been used as photosensitizers to generate ROS and were developed for image-guided PDT.
  • a commercial ROS indicator 2', 7'-dichlorodihydrofluorescein diacetate (H2DCFDA) , was used and is a fluorescein derivative and can recover its green fluorescence through oxidation by ROS.
  • ASCP-2P was compared with ASCP, TPE-PY, and TPE-IQ (FIG. 13) under irradiation of white light. Surprisingly, the fluorescent signals were saturated after 30 seconds of the irradiation in mixing with ASCP-2P. Other candidates were far away from the saturated intensity in 30 seconds of the irradiation (FIG. 12) .
  • the main reason of the poor ROS generation abilities of TPE-IQ and TPE-PY may be due to absorption. Their absorptions were shorter than 400 nm, meaning that most of the molecules were not excited under white light and less oxygen obtained the excited energy in the triplet state.
  • ASCP showed almost no ROS generation and ASCP-2P showed high ability in ROS generation (FIGS. 12-13) .
  • XTT assay was employed to evaluate the anticancer effect of ASCP-2P. As shown in FIG. 15, ASCP-2P without light exposure was almost non-toxic to A549 cells. There were nearly 90%cells alive even at the highest concentration (80 ⁇ M) . However, with exposure to white light for 1 min, ASCP-2P led to dose-dependent cell death. The IC 50 value was about 33 ⁇ M. In addition, co-treatment of NAC significantly attenuated the cytotoxic effect of ASCP-2P with light. For instance, 80 ⁇ M of ASCP-2P led to more than 90%cell death, while more than 75%cells were alive upon NAC co-treatment.
  • Clonogenic assay was performed to evaluate the radiosensitization effect of ASCP-2P.
  • ASCP-2P Prior to irradiation, A549 cancer cells were incubated with ASCP-2P (10 ⁇ M) for 2 h to ensure the targeting delivery of ASCP-2P to mitochondria. After that, irradiation was given at a series of doses (2, 4, and 6 Gy) . Cells were then immediately seeded into 6 well plates to study the colony forming ability.
  • ASCP-2P without light showed no radiosensitization effect when compared to irradiation alone.
  • the calculated SER10 was 1.62.
  • FIG. 16-17 showed that ASCP-2P with light was the most effective agent that could sensitize lung cancer cells to irradiation. There was a significant difference between the colony forming ability in cells treated with ASCP-2P and paclitaxel or GNP. As calculated from the curve, SER10 of paclitaxel was 1.32, while that of GNP was 1.19. Both were significantly lower than SER10 of ASCP-2P, which reached 1.62, the highest among the three agents.
  • NAC antioxidant agent
  • co-treatment of NAC substantially decreased the expression of anti-apoptotic Bcl-2 and strengthened the expression of the pro-apoptotic Bax and BAD after the exposure to ASCP-2P with light, which clearly demonstrated that the radiosensitization effect of ASCP-2P was closely related to the induction of intracellular ROS by light.
  • Compound 3 was utilized for lysosome targeting (FIG. 23) .
  • the selectivity was confirmed by commercial dye Lyso-tracker red. It can also be used for two photon imaging in order to give a higher resolution and high signal-to-noise ratio (FIG. 24) .
  • Compound 5 was used for lipid droplet imaging. In confocal images, it was found that the signals come from the whole cells. However, when the range for collection of emission is changed from 520 nm to 630 nm, the signals are found to only come from lipid droplets (FIG. 25) . This is due to the environment of lipid droplets being non-polar, which will shift the emission into more blue regions (FIG. 26) .

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Abstract

La présente invention concerne la synthèse et l'application de luminogènes AIE fluorescents rouges. La présente invention concerne des luminogènes AIE de ciblage mitochondrial, qui stimulent la radiosensibilité du carcinome pulmonaire. Les présents luminogènes AIE peuvent également cibler des membranes cellulaires, des gouttelettes lipidiques ou des lysosomes, ainsi que servir de radiosensibilisant en radiothérapie. La présente invention concerne en outre l'imagerie biphotonique avec des luminogènes AIE.
PCT/CN2016/105157 2015-11-10 2016-11-09 Luminogènes aie fluorescents rouges WO2017080449A1 (fr)

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WO2020253756A1 (fr) * 2019-06-18 2020-12-24 The Hong Kong University Of Science And Technology Composés fluorescents émissifs dans le rouge pour imagerie d'organites cellulaires
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