The development of efficient aggregation-induced emission (AIE) active probes is crucial for disease diagnosis, particularly for tumors and cardiovascular diseases. Current AIE-active probes primarily focus on improving their water solubility to resist aggregation, thereby achieving an initial fluorescence-off state. However, the complex biological environment can cause undesirable aggregation, resulting in false signals. To address this issue, we have ingeniously introduced an azo group into the AIE luminogen (AIEgen), developing a reductase-activated AIE probe, Azo-quinoline-malononitrile (QM)-PN, for imaging hypoxic environments. In this probe, the azo group promotes intramolecular motion through rapid E/Z isomerization, causing the excited state energy to dissipate via non-radiative decay, thus turning off the initial fluorescence. In the presence of reductase, Azo-QM-PN is reduced and cleaved to produce the hydrophobic AIEgen NH2-QM-PN, which subsequently aggregates and generates an in situ AIE signal, thereby imaging the hypoxic environment with reductase. Encapsulation of Azo-QM-PN with DSPE-PEG2000 results in the formation of the nanoprobe Azo-QM-PN NPs, which can effectively penetrate cell membranes, specifically illuminate tumor cells, monitor fluctuations in azo reductase levels, and deeply penetrate and image multicellular tumor spheroids, demonstrating potential for hypoxic tumor imaging. Additionally, the nanoprobe Azo-QM-PN NPs can selectively image hypoxic atherosclerotic plaque tissues, showing potential for detecting atherosclerosis. Therefore, in this study, we successfully developed an enzyme-activated AIE probe for imaging hypoxic environments, laying the foundation for further clinical applications.
Sonodynamic therapy (SDT) is garnering considerable attention as a promising treatment for deep-seated tumors because of its strong tissue penetration ability, non-invasiveness, and controllability. However, the SDT efficiency of traditional sonosensitizers including porphyrins and their derivatives are limited due to their poor water dissolubility, high aggregation, and low reactive oxygen species (ROS) production efficiency. Consequently, it is crucial to develop novel sonosensitizers with high yields of ROS, outstanding water solubility, and good biocompatibility. Herein, we constructed a new platform for SDT based on unimolecular porphyrin derivatives OPV-C3-TPP. The probe OPV-C3-TPP was synthesized by covalently linking conjugated oligomers (OPV) with 5, 10, 15, 20-tetra (4-aminophenyl) porphyrin (TAPP). The introduction of OPV greatly improves the water solubility of the porphyrins and reduces the self-aggregation of the porphyrins. In addition, OPV-C3-TPP has good intramolecular energy transfer efficiency, thus enhancing the yield of ROS. The experimental results show that OPV-C3-TPP exhibits excellent ROS generation capacity under ultrasound (US) irradiation, which leads to apoptosis and necrosis of tumor cells. In vivo tumor growth is also significantly inhibited in the OPV-C3-TPP + US group, exhibiting better SDT effects than TAPP. Therefore, the unimolecular OPV-C3-TPP can be used as a potential sonosensitizer, providing a promising SDT for deep-tissue tumors.
Covalent organic cages (COCs) are three-dimensional organic molecules with permanent cavities, known for their ordered pore structures, excellent processability, and modular design. They have shown significant potential in applications such as gas adsorption, molecular separation, and catalysis. Introducing chiral elements into COCs results in chiral COCs with confined chiral cavities, which endows them with unique chiral functions and expands their application prospects. This review summarizes the research progress on chiral covalent organic cages, focusing on strategies for incorporating chiral elements, the structures and synthesis methods of representative chiral COCs, and advancements in their chiral functions. Additionally, we provide perspectives on future research directions. We hope this review will inspire further interest and creativity among researchers in the field of chiral molecular cages, leading to the development of materials with unique structures and functions.
Donor-acceptor (D-A) compounds are particularly important in optoelectronic and biological applications. However, they are normally synthesized in the presence of transition metal catalysts. Herein, we report a metal-free method by a complex-mediated nucleophilic aromatic substitution of aryl nitriles with amines. The method can lead to rich D-A type aggregation-induced emission luminogens (AIEgens) with tunable properties. They emit from deep-blue to yellow-green and possess high photoluminescence quantum yields up to 70.5% in the aggregate state. Interestingly, the suppression of intramolecular flapping is proved to play an indispensable role in the AIE behavior, which is different from the mechanism met in other AIEgens. Moreover, the biocompatible AIEgens possess specific staining of lipid droplets in HeLa cells and the superiority of identifying fatty liver over traditional Oil Red O staining is exhibited.
Ferroptosis is a novel form of cell death driven by oxidative damage, and is implicated in various pathological conditions, including neurodegenerative diseases, retinal damage, and ischemia-reperfusion injury of organs. Inhibiting ferroptosis has shown great promise as a therapeutic strategy for these diseases, underscoring the urgent need to develop effective ferroptosis inhibitors. Although Ferrostatin-1 (Fer-1) is a potent ferroptosis inhibitor, its susceptibility to oxidation and metabolic inactivation limits its clinical utility. In this study, the accumulation of peroxides and the resulting oxidative damage in the cellular microenvironment during ferroptosis were utilized to design Ferrostatin-1 prodrugs with reactive oxygen species-responsive features. This approach led to the development of a series of ferroptosis inhibitors that were capable of recognizing oxidative damage in diseased areas, allowing for targeted release and improved stability. The novel compounds demonstrated significant inhibitory effects and selectivity against RSL-3-induced ferroptosis in HK-2 cells, with compound a1 exhibiting an EC50 of 15.4 ± 0.7 μM, outperforming Fer-1. These compounds effectively identify the oxidative microenvironment associated with ferroptosis, enabling the targeted release of Fer-1, which prevents lipid peroxide accumulation and inhibits ferroptosis. This strategy holds promise for treating diseases related to ferroptosis, offering a targeted and intelligent therapeutic approach.
Photodynamic therapy (PDT) has emerged as a promising protocol for cancer therapy. However, real-time monitoring of PDT progress and accurate determination of the optimal treatment timing remain challenges. In this work, we selected carbon dots (CDs) and new indocyanine green (IR820) as building units to fabricate a smart nanotheranostics (CDs-IR820 assembly) with the characteristics of controlled release and real-time imaging to solve the time gap between diagnosis and treatment. The fabricated CDs-IR820 assembly locked the photosensitivity of the CDs and could degrade under 750 nm laser irradiation to achieve controlled release of the CDs, thus used for cell imaging and producing single oxygen under the white light. Besides, the released CDs could migrate from the mitochondria to the nucleus during the PDT process, indicating the cell activity, which facilitated the regulation of treatment parameters to achieve the precise PDT for cancer.
The blood-brain barrier (BBB) is a substantial impediment to effectively delivering central nervous system (CNS) therapies. In this review, we provide a comprehensive dissection of the BBB's elaborate structure and function and discuss the inherent limitations of conventional drug delivery mechanisms due to its impermeability. We summarized the creative deployment of nanocarriers, the astute modification of small molecules to bolster their CNS penetration capabilities as well as the burgeoning potential of magnetic nanoparticles and optical techniques that are positioned to enable more precise and targeted drug delivery across the BBB and we discuss the current clinical application of some nanomedicines. In addition, we emphasize the indispensable role of artificial intelligence in designing novel materials and the paramount significance of interdisciplinary research in surmounting clinical challenges associated with BBB penetration. Our review meticulously integrates these insights to accentuate the impact of nanotechnological innovations in BBB research and CNS disease management. It presents a promising trajectory for the evolution of patient care in neurological disorders and suggests that these scientific strides could lead to more efficacious treatments and improved outcomes for those afflicted with such conditions.
Rational interface engineering via regulating the anchoring groups between molecular catalysts and light-absorbing semiconductors is essential and emergent to stabilize the semiconductor/molecular complex interaction and facilitate the photocarriers transport, thus realizing highly active and stable photoelectrochemical (PEC) water splitting. In this mini review, following a showcasing of the fundamental details of hybrid PEC systems containing semiconductor photoelectrodes and molecular catalysts for water splitting, the state-of-the-art progress of anchoring group regulation at semiconductor/molecular complex interface for efficient and stable PEC water splitting, as well as its effect on charge transfer kinetics, are comprehensively reviewed. Finally, potential research directions aimed at building high-efficiency hybrid PEC water splitting systems are summarized.
Metal-organic framework (MOF) has been widely used as filler of mixed-matrix membranes (MMMs) because of their tunable pore sizes, large surface areas, and rich functional groups. However, a relatively high diffusion barrier in the framework of bulk MOF fillers inevitably reduces gas permeability. Introduction of hierarchically porous structure represents an effective method for reducing guest diffusion resistance with no compromise in gas selectivity. In this study, hierarchical ZIF-8 (H-ZIF-8) was prepared using carboxylated polystyrene (PS-COOH) nanospheres as a hard template. Owing to the introduction of carboxyl groups, electrostatic interaction between PS nanospheres and Zn2+ ions is enhanced, facilitating uniform embedment of PS nanospheres in bulk ZIF-8 filler. After dissolution of PS-COOH nanospheres with dimethylformamide solvents, H-ZIF-8 with tunable textural properties is readily obtained. Gas permeation results indicate that compared with bulk ZIF-8 filler, fast diffusion pathways for guest molecules are established in H-ZIF-8 filler, resulting in a CO2/N2 separation factor (SF) of 48.77 with CO2 permeability of 645.76 Barrer in terms of H-ZIF-8 MMMs with 6 wt % loading, which well exceeds the 2008 Robenson upper bound for CO2/N2 gas pair, thus showing promising prospects for high-efficiency CO2 capture from flue gas.