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Non-invasive dynamic tracking of lysosomes and their interactions with other organelles is important for the study of lysosomal function and related diseases. However, many fluorescent dyes developed so far to target lysosomes cannot be used to monitor these processes due to the high concentrations required for imaging, long cell penetration times, and non-ideal photostability. In this regard, we synthesized three lysosomal targeting probes with large Stokes shifts, good stability, and high brightness. The Q-P-ARh dye, developed by us for the first time, can stain lysosomes at ultra-low concentrations (1.0 nM) without affecting the physiological functions of the lysosomes. More importantly, its excellent anti-interference ability and ultrafast lysosomal staining ability (within 1.0 min) clearly monitored the entire dynamic process of lipophagy. Ultimately, this method can greatly contribute to the study of autophagy pathways. This novel fluorescence platform shows great promise for the development of biological probes for application in pathological environments., (© 2021 Wiley-VCH GmbH.)

To maximize the utilization and response to the high oxidative stress environment of tumor sites while avoiding the dilemma of enhancing reactive oxygen species (ROS) response in a single way, mitochondrial targeting combined with fluorescent self-reporting polymeric nanocarriers ( 1K-TPP and 2K-TPP ) with grafted structures were synthesized via a chemoenzymatic method in a high yield to simultaneously enhance the drug delivery of endogenous ROS responses. 1K-TPP and 2K-TPP loaded doxorubicin (DOX) at a high content over 12% and formed homogeneous spherical micelles. In vitro , both of them showed promising high sensitivity (detection limit below 200 nM H 2 O 2 ), fast response, and ratiometric fluorescent self-reporting properties (fluorescent enhancement more than 200 times) to ROS and excellent stability under physiological conditions, while achieving a rapid release of the DOX in response to 1 mM H 2 O 2 . Cell co-localization experiments exhibited that they had favorable mitochondrial targeting, and mitochondrial isolation experiments also confirmed that the TPP-modified 1K-TPP selectively accumulated nearly three times in mitochondria than that in total cells. The internalization of 1K-TPP and 2K-TPP into cancer cells was greatly improved by nearly 200% compared to that of unmodified control ( 1K-OH and 2K-OH ) and also explored a unique energy-dependent endocytosis. Furthermore, stimulation of endogenous ROS enhanced the green fluorescence intensity (up to 51.4%) of the linked probe so as to destroy the internal structure of the nanocarriers, achieving self-reporting of the drug's intracellular release and tracking of the intracellular location of nanocarriers. The cytotoxicity of DOX-loaded 1K-TPP and 2K-TPP in tumor cells with a higher ROS content showed statistical superiority to that of 1K-OH and 2K-OH , benefiting from the extremely good endogenous ROS response sensitivity leading to the differential selective release of drugs. These results demonstrate the potential of 1K-TPP and 2K-TPP , especially for 1K-TPP , as mitochondria-targeted, fluorescent self-reporting nanocarriers for combined enhancement of endogenous ROS responsiveness.

The viscosity of lysosome is reported to be a key indicator of lysosomal functionality. However, the existing mechanical methods of viscosity measurement can hardly be applied at the cellular or subcellular level. Herein, a BODIPY-based two-photon fluorescent probe was presented for monitoring lysosomal viscosity with high spatial and temporal resolution. By installing two morpholine moieties to the fluorophore as target and rotational groups, the TICT effect between the two morpholine rings and the main fluorophore scaffold endowed the probe with excellent viscosity sensitivity. Moreover, Lyso-B succeeded in showing the impact of dexamethasone on lysosomal viscosity in real time.

Non‐invasive dynamic tracking of lysosomes and their interactions with other organelles is important for the study of lysosomal function and related diseases. However, many fluorescent dyes developed so far to target lysosomes cannot be used to monitor these processes due to the high concentrations required for imaging, long cell penetration times, and non‐ideal photostability. In this regard, we synthesized three lysosomal targeting probes with large Stokes shifts, good stability, and high brightness. The Q‐P‐ARh dye, developed by us for the first time, can stain lysosomes at ultra‐low concentrations (1.0 nM) without affecting the physiological functions of the lysosomes. More importantly, its excellent anti‐interference ability and ultrafast lysosomal staining ability (within 1.0 min) clearly monitored the entire dynamic process of lipophagy. Ultimately, this method can greatly contribute to the study of autophagy pathways. This novel fluorescence platform shows great promise for the development of biological probes for application in pathological environments. [ABSTRACT FROM AUTHOR]

The SiO2@SiO2:Tb(1,2‐BDC)3phen microspheres with monodispersed core‐shell structure, are kind of fluorescent particles, which are prepared by a seeded growth method under the catalysis of glacial acetic acid (1,2‐BDC, 1,2‐benzenedicarboxylic acid; phen, 1,10‐phenanthroline). Firstly, silica seed was fabricated by the hydrolysis of ethyl orthosilicate, and the Tb(1,2‐BDC)3phen was prepared by using 1,2‐BDC and phen. Then, a thin mesoporous silica shell doped with Tb(1,2‐BDC)3phen was grown on the prepared monodisperse silica colloids. The prepared phosphor was analyzed by Fourier‐transform infrared spectroscopy, X‐ray diffraction analysis, scanning electron microscopy, transmission electron microscopy, thermogravimetric and fluorescence spectroscopy. The experimental results showed that the diameter of the SiO2@SiO2:Tb((1,2‐BDC)3phen microsphere was about 200 nm with a typical core‐shell structure, among which the diameter of the silica core was 180 nm, and that of the mesoporous silicon shell doped with terbium complex was about 10 nm. The fluorescence intensity of SiO2@SiO2:Tb((1,2‐BDC)3phen microsphere is nearly three times higher than that of Tb((1,2‐BDC)3phen complexes. The prepared microspheres could be widely used in bio‐imaging, optoelectronic appliances and medical diagnosis. [ABSTRACT FROM AUTHOR]

[Display omitted] To minimize unwanted reactions with high concentrations of reduced glutathione (GSH) in the tumor microenvironment (TME) during chemodynamic therapy (CDT), a simple and effective strategy was developed to fabricate a TME stimuli-responsive theranostic nanomedicine (Fe-CD) for fluorescence imaging-guided GSH depletion and cancer therapy by combining fluorescent imaging carbon dots (CD) and Fe(III). Introducing Fe(III) into Fe-CD not only quenched the fluorescence of CD while reacting with and consuming intracellular GSH for fluorescence imaging of the depletion of GSH but also provided a source of metal ions to generate more abundant hydroxyl radicals (•OH) with hydrogen peroxide (H 2 O 2) through the Fenton reaction to improve CDT. Fe-CD showed promising •OH generation under H 2 O 2 to effectively degrade methylene blue in vitro and obviously activate the green fluorescence of the reactive oxygen species (ROS) probe in cells. Benefiting from the fluorescence enhancement in response to TME stimulation, Fe-CD greatly enhanced CDT cytotoxicity while monitoring successful GSH depletion by fluorescence imaging. Fe-CD has the potential to act as a theranostic nanomedicine for fluorescence imaging-guided GSH depletion to amplify CDT. [ABSTRACT FROM AUTHOR]

More evidence supports that endoplasmic reticulums stress (ER stress) has close relationship with many disease, including Alzheimer's disease, and such diseases are often closely related to senescence. Both ER stress and senescence involve disorder of redox regulation and may further cause ClO- accumulation. It is of great importance to develop a tool to visualize ralated organelles to investigate the role of ClO- during ER stress or senescence. In this work, a novel dual-targetable ClO- probe RT-ER was designed, and the probe could image endoplasmic reticulums and lysosome by sequence under stimulation of ClO-. RT-ER worked in a ratiometric manner and was extremely sensitive to ClO-(~ 484 folds enchancement within 10 s after the stimulation of ClO-). RT-ER showed great biocompatibility and was further applied in living cells imaging. We demonstrated that RT-ER enables both exogenous and endogenous ClO- imaging. Compared with the commercial dye Lysosome-Tracker Deep Red, RT-ER showed better photobleaching resistance. We successfully used RT-ER to track the interaction between endoplasmic reticulum and lysosome after ClO- accumulation. More importantly, with the help of RT-ER, we further revealed the level of ClO- change during ER stress and senescence, which will facilitate the functional study of ClO- −disease contacts. [Display omitted] • The probe could image ERs and lysososme in two channels by sequence with stimulation of ClO-. • The intereactions between lysosome and ER can be long-term tracked by the probe when ClO- continue to accumulate in cells. • The fluctuation of ClO- during ERs stress and senescence can be monitored by the probe. [ABSTRACT FROM AUTHOR]

• A compound with an AIEgen was firstly synthesized as a G-quadruplex probe. • A efficient and zero background analytical method was successfully developed for the detection of G-quadruplex DNA. • With the help of the probe, DNA with G-quadruplex structures in mitochondrion can be easily, quickly and accurately tracked without further washing operations. Inspired by the mechanism of aggregation induced emission, two derivatives of thiazole orange (TPE-mTO and Ph-TO) were rationally designed and prepared in this work. Their selectivity and sensitivity towards G-quadruplex were studied by fluorescence titration, gel analysis, and circular dichroism (CD) experiments. TPE-mTO could selectively lights-up G-quadruplex DNA structures with no conformational transition, while Ph-mTO could not distinguish the G-quadruplex DNA structure from other nucleic acid, which probably owing to the pocket size and shape of the G-quadruplex DNA only could hinder the rotation of TPE moiety. Then the speculation was verified by molecular docking, TPE-mTO could adopt an appropriate pose in 3′ and 5′ binding pockets of CM22 (G-quadruplex), the multiple interaction between TPE-mTO and CM22 do hinder the rotation of TPE moiety and lead to strong fluorescence. In addition, the detection limit (DL) of TPE-mTO towards CM22 (prefolded G-quadruplex) was found as low as 4.1 nM. With the help of TPE-mTO , the G-quadruplex DNA structures in mitochondrion can be easily and quickly tracked without further washing operations. Overall, the probe we developed (TPE-mTO) was a simple but powerful tool for studying G-quadruplex structures. [ABSTRACT FROM AUTHOR]