A "dual-key-and-lock" platform for distinguishing autophagy during neuroinflammation.

Autophagy is an essential degradative process that governs the renewal of organelle and maintains the homeostasis of cellular microenvironment. Its dysregulation has been demonstrated to be an indicator for neuroinflammation. To elucidate the interrelationship between neuroinflammation and autophagy, optical probes are ideal tools as they offer a number of advantages such as high spatiotemporal resolution and non-invasive sensing, which help to visualize the physiological and pathological functions of interested analytes. However, single autophagy parameter-response probes may generate false-positive results since they cannot distinguish between neuroinflammation and other autophagic stimuli. In contrast, chemosensors that respond to two (or more) targets can improve selectivity by qualifying response conditions. Herein, a "dual-key-and-lock" strategy was applied to construct probe (Vis-NO) to selectively recognize autophagy under inflammation out of other stimuli. The red fluorescence of Vis-NO was lit up only in the simultaneously presence of high viscosity and nitric oxide (NO) in lysosome. Due to the characteristics of high viscosity and overexpressed NO within lysosomes, Vis-NO could be used to selectively identify autophagy during neuroinflammation, providing expanding insights into the interrelationship between autophagy, neuroinflammation and stroke in pathology, and informing about the mechanisms through which autophagy regulates inflammation.

1,3-diene-based AIEgens: Stereoselective synthesis and applications.

In recent years, significant advancements have been made in the synthesis and application of 1,3-dienes. This specific structural motif has garnered significant attention from researchers in materials science and biology due to its unique aggregation-induced emission (AIE) properties and extensive conjugation systems. The luminescent characteristics of these compounds are notably influenced by the geometry of the two double bonds. Therefore, it is essential to consolidate stereoselective synthetic strategies for 1,3-dienes. This comprehensive review seeks to elucidate the diverse techniques employed to attain stereo-control in the synthesis of 1,3-diene-based AIE luminogens (AIEgens). Particular emphasis is placed on comprehending the determinants of stereoselectivity and exploring the array of substrates amenable to these methods. Furthermore, the review underscores the AIE properties exhibited by these compounds and their extensive utility in organic light-emitting diodes (OLEDs), stimuli-responsive materials, sensors, bioimaging, and photodynamic therapy (PDT).

Pancreatic cancer environment: from patient-derived models to single-cell omics.

Pancreatic cancer (PC) is a highly malignant cancer characterized by poor prognosis, high heterogeneity, and intricate heterocellular systems. Selecting an appropriate experimental model for studying its progression and treatment is crucial. Patient-derived models provide a more accurate representation of tumor heterogeneity and complexity compared to cell line-derived models. This review initially presents relevant patient-derived models, including patient-derived xenografts (PDXs), patient-derived organoids (PDOs), and patient-derived explants (PDEs), which are essential for studying cell communication and pancreatic cancer progression. We have emphasized the utilization of these models in comprehending intricate intercellular communication, drug responsiveness, mechanisms underlying tumor growth, expediting drug discovery, and enabling personalized medical approaches. Additionally, we have comprehensively summarized single-cell analyses of these models to enhance comprehension of intercellular communication among tumor cells, drug response mechanisms, and individual patient sensitivities.

Six-Membered Aromatic Nitrogen Heterocyclic Anti-Tumor Agents: Synthesis and Applications.

Cancer stands as a serious malady, posing substantial risks to human well-being and survival. This underscores the paramount necessity to explore and investigate novel antitumor medications. Nitrogen-containing compounds, especially those derived from natural sources, form a highly significant category of antitumor agents. Among these, antitumor agents with six-membered aromatic nitrogen heterocycles have consistently attracted the attention of chemists and pharmacologists. Accordingly, we present a comprehensive summary of synthetic strategies and clinical implications of these compounds in this review. This entails an in-depth analysis of synthesis pathways for pyridine, quinoline, pyrimidine, and quinazoline. Additionally, we explore the historical progression, targets, mechanisms of action, and clinical effectiveness of small molecule inhibitors possessing these structural features.

Two-photon imaging for visualizing polarity in lipid droplets during chemotherapy induced Ferroptosis.

As a novel pattern of regulated cell death (RCD), Ferroptosis is induced by lipid peroxide-dependent iron accumulation, which is associated with reactive oxygen species (ROS). Ferroptosis regulates cell death via ROS accumulation-related lipid peroxides accumulation, affecting the structure and polarity of lipid droplets (LDs). Compared with reactive fluorescent probes, environment-sensitive fluorescent probes allow for maximum preservation of the intracellular environment while monitoring metabolic activity in situ, resulting in more accurate monitoring results. In this study, a polarity-sensitive two-photon fluorescent probe with anchoring capacity in LDs, LIP-Pola, is reported and applied to monitor the polarity of LDs during cell Ferroptosis by in situ imaging analysis of cell Ferroptosis via LDs polarity changes. Additionally, Paclitaxel is shown to increase the Ferroptosis level from data of cells and tumor tissue sections, suggesting that Paclitaxel may deactivate tumor cells by regulating Ferroptosis.

Tracking autophagy process with a through bond energy transfer-based ratiometric two-photon viscosity probe.

Autophagy is a self-degradation process in cells, which is of vital significance to the health and operation of organisms. Due to the increase of lysosomal viscosity during autophagy, viscosity probes that specifically accumulate in lysosome are powerful tools for monitoring autophagy and investigating related diseases. However, there is still a lack of viscosity-sensitive ratiometric autophagy probes, which restricts the tracking of autophagy with high accuracy in complex physiological environment. Herein, a viscosity-responsive, lysosome targeted two-photon fluorescent probe Lyso-Vis was designed based on through bond energy transfer (TBET) mechanism. The TBET-based probe achieved the separation of two emission baselines, which greatly improved the resolution and reliability of sensing and imaging. Under 810 nm two-photon excitation, the emission intensity ratio of the red and green channel increased with a viscosity dependent manner. Lyso-Vis not only for the first time realized ratiometric sensing of lysosomal viscosity during autophagy process, but also visualized the association of autophagy with inflammation and stroke, and it was applied to explore the activation and inhibition of autophagy during stroke in mice.

A new strategy to construct gold nanocluster-based optical probes using luminescence resonance energy transfer.

Monolayer-protected metal nanoclusters (MPCs) are emerging as intriguing luminescent materials, but the construction of MPC-based optical probes is still scarce because of both the limited photoluminescence efficiency of MPCs and the lack of recognition mechanism. We herein propose a luminescence resonance energy transfer-based strategy to circumvent these problems.

Gold nanoclusters as a GSH activated mitochondrial targeting photosensitizer for efficient treatment of malignant tumors.

Gold nanoclusters (Au NCs), which have the characteristics of small size, near infrared (NIR) absorption and long triplet excited lifetime, have been used as a new type of photosensitizer for deep tissue photodynamic therapy (PDT). However, the therapeutic efficiency of the nano-system based on Au NCs still needs to be improved. Herein, we proposed a strategy using Mito-Au25@MnO2 nanocomposites to achieve enhanced PDT. Au25(Capt)18 - nanoclusters were applied as photosensitizers and further modified with peptides to target mitochondrial and MnO2 nanosheets to consume glutathione (GSH). In the presence of GSH, Mito-Au25@MnO2 dis-integrated and Mito-Au25 nanoparticles realized accurate mitochondrial targeting. Under the irradiation of 808 nm light, the nanocomposite ensured highly efficient PDT both in vitro and in vivo via oxidation pressure elevation and mitochondrial targeting in cancer cells.

Deep imaging for visualizing nitric oxide in lipid droplets: discovering the relationship between nitric oxide and resistance to cancer chemotherapy drugs.

A near-infrared two-photon fluorescent probe (TAN) was synthesized for selective detection and deep-depth imaging of NO in lipid droplets. All results demonstrated that NO production in lipid droplets is closely correlated with the resistance to anti-tumor drugs, and NO inhibitors can effectively improve the efficacy of chemotherapeutic agents.

Developing a ratiometric two-photon probe with baseline resolved emissions by through band energy transfer strategy: Tracking mitochondrial SO2 during neuroinflammation.

Sulfur dioxide (SO2) with the largest quantity and widest distribution in the atmosphere is closely related to many nervous system diseases via mitochondria respiration. It is of great significance to monitor this gaseous molecule during various physiological and pathological processes, but currently the task still remains challenging due to the lack of reliable tools. Through-bond energy transfer (TBET) is a relatively new strategy to fabricate ratiometric fluorescent probes, which does not need spectral overlap between the energy donor and acceptor while provides high energy-transfer efficiency. It offers strong dual fluorescence emission peaks as well as large wavelength differences between the two peaks, which increases the bioimaging resolution and reliability. Herein, we developed a TBET-based ratiometric probe (TBET-SO2) with a series of superior properties for in vivo SO2 imaging. Excited by near-infrared pulsed laser (810 nm), the probe undergoes TBET and produces far-red emission (611 nm). It achieved significant energy-transfer efficiency (90.5%) and large spectral gap between two peaks (△λ = 118 nm). Upon reacting with SO2, TBET-SO2 showed ~30-fold enhancement of ratiometric signal contributed by the baseline resolved emissions. A detection limit of as low as 0.09 µM was obtained. Furthermore, TBET-SO2 was successfully applied for visualizing the mitochondrial SO2 in living cells and mice brain tissue during the neuroinflammation process induced by SO2 pollution.

Lighting Up NIR-II Fluorescence in Vivo: An Activable Probe for Noninvasive Hydroxyl Radical Imaging.

The detection of hydroxyl radical (·OH) in vivo faces challenges as ·OH has short lifetime and low concentration in the body. Fluorescence imaging within the second near-infrared window (NIR-II, 1000-1700 nm) is a promising approach to in vivo organ and tissue imaging, but ·OH fluorescent probes emitting at this region have not been reported up to now because of the difficulty of probe design. Herein, we report the strategy to fabricate the first NIR-II probe for ·OH by directly breaking/recovering the conjugated system and rigid planar structure of an organic fluorophore, which could regulate the fluorescence intensity regardless of emission wavelength. This activable probe, Hydro-1080, emitted in 1000-1400 nm after responding to ·OH. Hydro-1080 exhibited excellent sensitivity (LOD = 0.5 nM) and selectivity to ·OH. It was able to track subtle variation of [·OH] in liver induced by external stimuli and offered clear images with high contrast. This work also indicates that this simple and straightforward strategy can be extended to develop NIR-II fluorescent probes efficiently.