In kidney organoids, typically only the basal membrane is exposed, limiting toxicity assessments of apically transported drugs. Although the reversion of basal-out organoids has successfully created apical-out organoids of the intestine and airway, this method has not yet been applied to kidney organoids. Here, a technique to reverse tubuloid polarity is reported, enabling the apical surface to evert and face the medium by dissolving extracellular matrix proteins in the culture system. The resulting apical-out tubuloids maintain high viability, exhibit proper morphological characteristics, and express cell adhesion proteins and biomarkers appropriately. Further analyses, including RNA sequencing and scanning electron microscopy, confirm the presence of primary cilia on the outer surface, along with albumin receptors and Na⁺/K⁺-ATPase on the outer and inner surfaces, respectively, and apical proteins such as zonula occludens-1 on the lateral membrane, verifying the apical-out orientation. These apical-out tubuloids demonstrate selective albumin internalization, greater sensitivity to apically transported colistin, and reduced sensitivity to basally transported tenofovir, effectively mimicking drug transport mechanisms. This approach for generating apical-out tubuloids is a valuable tool for assessing drug efficacy and toxicity in physiologically relevant, tissue-like microenvironments, significantly advancing the field of nephrotoxicity research.

While chirality is a prevalent character of numerous biological and synthetic organic molecules, its selective absorption of circularly polarized light, known as circular dichroism (CD), is typically small due to intrinsically weak coupling between magnetic and electric dipoles. However, thin films of aggregated, enantiopure prolinol-derived squaraine molecules (ProSQ-C16) exhibit an unusually large excitonic CD signal, although the underlying mechanism is not yet known. In this study, we employ steady-state and ultrafast transient absorption spectroscopy to investigate the nature and dynamics of excitons in aggregates of enantiopure and racemic ProSQ-C16 thin films. Highly resembling transient responses of enantiopure thin films under excitations at different photon energies strongly indicate that a single type of aggregate dominates the linear optical response, that is, a strong red-shifted (J-like) and weak blue-shifted (H-like) absorption band. On the other hand, the transient properties of the racemic thin film deviate from this pattern and remain largely ambiguous. The short lifetime of excited states and coherent oscillations present in the dynamics of the transient absorption signal indicate that the early time dynamics are governed by a transition towards a dark intermediate state, which might arise from intermolecular charge transfer with potential contributions from the coupling of excitons to the vibrations. This non-radiative relaxation pathway explains the unusually weak fluorescence of the predominately J-like behaving aggregate. Our findings conclusively show that the chiral aggregate structure has a strong impact on the optical and dynamic response of the excitons and underline the significance of non-Frenkel exciton states for the optical properties of anilino squaraine dyes.

Physically unclonable functions (PUFs) are essential for anticounterfeiting. Creating high-stability, multimode, and secure labels remains challenging. Herein, we present a novel self-assembly method for modulating the optical signals of rare-earth (RE) complexes via interactions with Ag nanoparticles (Ag-NPs). Initially, we engineered a positively charged Eu³⁺ complex ([EuL₃]³⁺), which promotes the self-assembly of negatively charged Ag-NPs to form Eu/Ag-NPs composites. The assembly of Ag-NPs induces a surface plasmon effect that boosts the luminescent quantum yield and Raman signal intensities, and modifies the luminescence lifetime of the [EuL₃]³⁺. Crucially, these micron-scale Eu/Ag-NPs can be applied to substrates, facilitating high-resolution signal acquisition and diverse information encoding within limited space. Validation experiments reveal that PUF labels crafted using Eu/Ag-NPs exhibit inherent randomness and uniqueness, along with stable and repeatable signal output. The strategic self-assembly of Ag-NPs, mediated by [EuL₃]³⁺, along with the effective modulation of material properties, paves the way for advancing high-resolution, high-information-density solutions in anticounterfeiting technologies.

The accurate and sensitive detection of low-abundance cancer-related biomarkers in blood remains a key technical challenge in clinical applications. Herein, a simple and accurate sandwich-type electrochemical immunosensor based on a stable hydrogen-bonded cobalt-porphyrin framework (Co-HOF) was successfully developed for the ultrasensitive detection of the cancer-related biomarker, carcinoembryonic antigen (CEA). The antibody-modified Co-HOF forms a sandwich structure with the CEA aptamer electrode exclusively in the presence of CEA, enabling the specific electrochemical detection of CEA. The electrochemical signal increased linearly with the concentration of CEA, demonstrating a wide linear range (0.001–50 ng mL⁻¹) and a low detection limit (0.22 pg mL⁻¹), surpassing the performance of commercial ELISA kits and most reported detection methods. The sensor was successfully employed for CEA detection in spiked human serum, with recoveries ranging from 85.04% to 105.20%. Additionally, we collected blood samples from colorectal cancer patients and healthy individuals to clinically validate the sensor, observing that CEA levels increased with cancer progression. The sensor detection results showed strong consistency (R² = 0.995) with those obtained from commercial ELISA kits, demonstrating the proposed sensor's practicality for clinical detection of CEA and related cancer biomarkers.

The rapid development of internal light-driven photodynamic therapy stems from its capability to eliminate bulky physical light sources, addressing the medical requirements for comfort and portability in long-term diabetic wound management. To overcome limitations such as tissue penetration depth and controllability of internal light sources, this study introduces an antibacterial gel electrochemiluminescence device for the treatment of diabetic wounds and the monitoring of wound bacteria. We deploy a large-area luminescent device combining flexible screen-printed electrodes and a dual-network hydrogel, in which photodynamic therapy is driven by Ru@COFs' nanoconfinement-enhanced near-infrared electrochemiluminescence to achieve a deeper and safer antibacterial effect. The custom-sized screen-printed electrodes inherit the inborn electrochemical sensing function and enable intimate contact between reactive oxygen species and the wound. The device avoids physical light sources and provides a new paradigm for developing miniaturized integrated diagnostic and therapeutic wearable devices.

Phosphorus-containing functional materials have diverse applications in optoelectronics and bioscience owing to their unique properties. However, polycyclic π-conjugated phosphonium salts have been rarely explored due to their complex synthesis. In this work, a facile and efficient method for constructing polycyclic π-conjugated phosphonium salts (TBPIMe derivatives) is proposed, based on the photocyclization of phosphindolium salts (TPPIMe derivatives). Systematic experimental and theoretical investigations reveal the changed photophysical and photochemical properties when TPPIMe derivatives are converted to TBPIMe derivatives. Notably, the novel polycyclic π-conjugated phosphonium salt p-MOTBPIMe exhibits improved reactive oxygen species generation ability and much stronger specific affinity toward DNA than phosphindolium salts p-MOTPPIMe. Moreover, in vitro experiments demonstrate that p-MOTPPIMe can also be efficiently converted into p-MOTBPIMe under 405 nm laser irradiation in living cells, accompanied by the migration from cytoplasm to nucleus to enhance the photodynamic effect. Additionally, p-MOTBPIMe shows superior antibacterial activity against not only Gram-positive drug-resistant bacteria but also fungi, by leveraging both dark and light cytotoxicity. This work opens up a new chemical toolkit for novel polycyclic π-conjugated phosphonium salts, which are promising for developing advanced theranostic agents with satisfactory accuracy and efficacy.

Photodynamic therapy (PDT) and photothermal therapy (PTT) have emerged promising applications in both fundamental research and clinical trials. However, it remains challenging to develop ideal photosensitizers (PSs) that concurrently integrate high photostability, large near-infrared absorptivity, and efficient therapeutic capabilities. Herein, we reported a sample engineering strategy to afford a benzene-fused Cy5 dimer (Cy-D-5) for synergistically boosting PDT/PTT applications. Intriguingly, Cy-D-5 exhibits a tendency to form both J-aggregates and H-aggregates in phosphate-buffered saline, which show a long-wavelength absorption band bathochromically shifted to 810 nm and a short-wavelength absorption band hypsochromically shifted to 745 nm, respectively, when compared to its behavior in ethanol (778 nm). Density-functional theory calculations combined with time-resolved transient optical spectroscopy analysis reveal that the fused dimer Cy-D-5 exhibits a low ΔE_ST (0.51 eV) and efficient non-radiative transition rates (12.6 times greater than that of the clinically approved PS-indocyanine green [PS-ICG]). Furthermore, the Cy-D-5 demonstrates a higher photosensitizing ability to produce ¹O₂, stronger photothermal conversion efficiency (η = 64.4%), and higher photostability compared with ICG. These combined properties enable Cy-D-5 to achieve complete tumor ablation upon 808 nm laser irradiation, highlighting its potential as a powerful and dual-function phototherapeutic agent. This work may offer a practical strategy for engineering other existing dyes to a red-shifted spectral range for various phototherapy applications.

Carbon quantum dots (CQDs) represent a rapidly emerging class of nanomaterials with significant potential in biomedical applications due to their tunable fluorescence, high biocompatibility, and versatile functionalization. This review focuses on the recent progress in utilizing CQDs for drug delivery, bioimaging, biosensing, and cancer therapy. With their unique optical properties, such as tunable fluorescence, high quantum yield, and photostability, CQDs enable precise bioimaging and sensitive biosensing. Their small size, biocompatibility, and ease of surface functionalization allow for the development of targeted drug delivery systems, enhancing therapeutic precision and minimizing side effects. In cancer therapy, CQDs have shown potential in photodynamic and photothermal treatments by generating reactive oxygen species under light exposure, selectively targeting cancer cells while sparing healthy tissues. Furthermore, CQDs’ ability to penetrate biological barriers including the blood–brain barrier opens new possibilities for delivering therapeutic agents to hard-to-reach areas, such as tumors or diseased tissues. However, challenges such as optimizing synthesis, ensuring long-term stability, and addressing safety concerns in biological environments remain critical hurdles. This review discusses current efforts to overcome these barriers and improve CQD performance in clinical settings, including scalable production methods and enhanced biocompatibility. As research progresses, CQDs are expected to play an important role in improving healthcare by offering more targeted treatment options and contributing to advancements in personalized medicine.

Long-term in vivo fluorescence analysis is growing into a sparkling frontier in gaining deep insights into various biological processes. Exploration of such fluorophores with high performance still remains an appealing yet significantly challenging task. In this study, we have elaborately integrated a second near-infrared (NIR-II) emissive fluorophore with the metal Pt into a self-assembled prism-like metallacage M-DBTP, which enables the intravital long-term tracking of the metal Pt through NIR-II fluorescence imaging technologies. In addition, the intravital bioimaging of the metallacage-loaded nanoparticles (NPs) indicated an extraordinary photographic performance on the mice blood vessels and the rapid clearance of M-DBTP NPs from the blood within 7 h. The subsequent transfer to the bones and the retention of NPs in the bone marrow region for up to 35 days was revealed by long-term fluorescence analysis, which was confirmed by the distribution and metabolism of Pt through an inductively coupled plasma optical emission spectrometer. Moreover, the bright emission of M-DBTP NPs in the NIR-II region enables them to well perform on fluorescence imaging-guided tumor surgery.

Vibrio vulnificus is a highly virulent Gram-negative bacterium exhibiting extensive resistance to various antibiotics, presenting significant challenges for efficient and selective eradication. Recently, photosensitizer (PS)-based photodynamic therapy has emerged as an effective strategy against bacteria and biofilms. However, traditional PS struggles to penetrate the unique membrane structure of Gram-negative bacteria such as V. vulnificus, while avoiding traversal of the membrane barrier of eukaryotic cells. To address this issue, herein, a PS named BDTP with aggregation-induced emission properties was developed. BDTP can specifically target the DNA of V. vulnificus, but integrate into the cell membrane, preventing damage to the contents in eukaryotic cells due to its hydrophilic/lipophilic “Y-shaped” structural characteristics. In dark conditions, BDTP functions as an antibiotic, inhibiting bacterial proliferation. Upon white light stimulation, BDTP can induce phototoxic damage to the DNA of V. vulnificus and effectively inhibit/clear V. vulnificus biofilms. Additionally, the eukaryotic cell membrane barrier significantly reduces PS-induced damage to its nucleic acids. This strategy significantly promotes the healing of infected wounds in V. vulnificus-infected mice. Our work introduces the first PS targeting V. vulnificus-associated infections, demonstrating efficacy both in vitro and in vivo.

The aggregation of α-synuclein (ɑ-syn) coupled with overexpressed neuroinflammation instigates the degeneration of dopaminergic neurons, thereby aggravating the progression of Parkinson's disease (PD). Herein, we introduced a series of hydrophobic amino acid–based carbon dots (CDs) for inhibiting ɑ-syn aggregation and mitigating the inflammation in PD neurons. Significantly, we show phenylalanine CDs (Phe-CDs) could strongly bind with ɑ-syn monomers and dimers via hydrophobic force, maintain their stability, and inhibit their further aggregates in situ and in vitro, finally conferring neuroprotection in PD by rescuing synaptic loss, ameliorating mitochondrial dysfunctions, and modulating Ca²⁺ flux. Importantly, Phe-CDs demonstrate the ability to penetrate the blood–brain barrier (BBB), significantly improving motor performance in PD mice. Our findings suggest that Phe-CDs hold great promise as a therapeutic agent for PD and the relative neurodegenerative disease.

Circularly polarized luminescent materials find extensive applications in 3D displays, information encryption, and photoinduced supramolecular chirality. However, controlling the handedness of circularly polarized luminescence remains a significant challenge in advancing optical technologies. In this study, we present a Janus circularly polarized light emitter comprising a fluorescent film combined with chiral nematic cellulose with switchable chirality. The emitter achieves maximum luminescence dissymmetry factors (0.28 and −0.65) through mode switching. In addition, we show the emitter's versatility in inducing chiral helices in azobenzene polymers with varying polar groups, resulting in significant chiral signals. Importantly, the chirality of these polymers can be switched by altering the luminescence mode of the emitter. These results are expected to facilitate the efficient design of chiral luminescent materials and photoinduction devices.

The idea of preparation a water-soluble Pt-containing AIEgen was successfully realized by direct reversible addition-fragmentation transfer copolymerization of a Pt(II) complex (LPtPV) containing a vinyl group and polyvinylpyrrolidone (p(VP)). The resulting block-copolymer p(VP-b-LPtPV) containing 5–8 Pt(II) chromophores exhibits intriguing photophysical properties—strong solvent and concentration dependence of absorption and emission characteristics. Various physicochemical and analytical methods (NMR spectroscopy, XRD analysis, ESI-MS, AUC, DLS, ICP-OES, GPC, viscometry, TEM) were used to characterize the initial complex, its binuclear analogs, p(VP) and p(VP-b-LPtPV). The obtained data indicate that the photophysical properties of the latter are dictated by the type of aggregation process rather than solvatochromic effects. It is shown that at low concentration in organic solvents, the platinum chromophores aggregation is either absent (dimethylformamide) or occurs predominantly at intramolecular level (MeCN), whereas in aqueous media, p(VP-b-LPtPV) readily aggregates into micellar-type nanoparticles with a hydrophilic p(VP) corona and a hydrophobic Pt-containing core, in which strong intra- and intermolecular Pt···Pt and/or π···π interactions result in a significant red shift of absorption and emission down to 600 and 816 nm, respectively. Despite of emission shift into NIR area where emission is commonly quenched by nonradiative vibrational relaxation, an increase in the emission quantum yield occurs in complete agreement with the typical aggregation-induced emission (AIE) emitters’ behavior. Quantum mechanics/molecular mechanics simulations of aggregation processes also confirm the trends in the relationship between aggregation mode and photophysical behavior, particularly, in the variations of energy gaps between the ground state of the AIEgens and their excited singlet and triplet states.

Contagious diseases caused by different types of highly contagious pathogens, such as SARS-CoV-2, monkeypox virus, Mycobacterium tuberculosis, and human immunodeficiency virus, could trigger global outbreaks and bring a huge public health burden. Advanced diagnostic, therapeutic, and preventive strategies are urgently needed to deal with the epidemic of contagious diseases. Aggregation-induced emission (AIE) has emerged as one of the promising candidates that exhibit tunable photophysical properties, high biocompatibility, exceptional photostability, and a distinguishing aggregation-enhanced fluorescence. As a result, they offer effective strategies for the diagnosis, treatment, and prevention of contagious diseases. This review systematically outlined the latest research progress of AIE-based biomaterials and mechanisms in contagious diseases. The versatility of AIE molecules, as well as highly efficient fluorescence properties, has the potential to offer innovative strategies to combat these health challenges. Thanks to recent advances in materials science and a better understanding of aggregation-induced emission luminogens (AIEgens), AIEgens have great potential to provide better solutions for the treatment, detection, and prevention of contagious diseases. By reviewing state-of-the-art methods for the killing, detection, and prevention of contagious agents and highlighting promising technological developments, this outlook aims to promote the development of new means for the prevention and control of emerging, re-emerging, and major contagious diseases as well as further research and development activities in this critical area of research.

The restriction of the molecular motion has been extensively exploited in tailoring the photoluminescence (PL) of metal nanoclusters, while the activation of such a restriction at the molecular level remains highly challenging. In this work, a two-step strategy, that is, surface activating and surface coupling, was proposed to induce the restriction of the molecular motion of nanoclusters at the molecular level, and the corresponding nanoclusters underwent emission appearance and enhancement. The peripheral phosphine ligand functionalization and alkali metal cation introduction gave rise to a series of structural-correlated M⁺-incorporated Cu₁₄ nanoclusters (M = Li, Na, K, Rb, Cs) with a surface-aggregation characteristic, among which the K⁺-participating nanocluster displayed the strongest fluorescence intensity in both solution and crystal states. Atomic-level structure–property correlations were investigated to rationalize the PL comparisons. Overall, this work offers a new perspective for regulating the PL of metal nanoclusters via restricting their molecular motions, hopefully providing insight into the fabrication of highly emissive metal nanoclusters and cluster-based nanomaterials.

Luminescent probes attract increasing attentions for the unique superiorities like visually real-time detecting. However, for optical humidity sensing, it is still quite challenging to attain facile dehydration/activation in sensing materials, due to the high polarity of water molecules, which limits their applications in real-time detection and energy-conserving applications. Here, we report two fluorescent hydrogen-bonded organic frameworks (HOFs), HPISF-H₂O and TPISF. HPISF-H₂O achieves water absorption in low humidity, but needs an energy-intensive step (heating to ∼92°C in air) to dehydrate. Conversely, despite only a hydroxyl group being replaced, TPISF cannot bind to H₂O at all. In other words, real-time detection is not readily achieved through straightforward molecular design. Therefore, we propose a cocrystallization strategy to adjust their water-binding capacity. As a result, the HOF cocrystals are adjusted to have both good H₂O absorptivity and very gentle desorbing operation without heating (dry gas blowing or vacuuming). Benefiting from this strategy, appreciable advantages for an effective humidity sensor are realized, including real-time detection (second-scale response/recovery) and distinguishing fluorescence variation. Efficient sensing across a broad relative humidity (RH) range (10.0%–80.0%) was further achieved. Moreover, the mechanistic insight of fluorescent sensing was ascertained through detailed analyses of structural transformation, spectroscopic data, and theoretical approach.

Broad-spectrum photodetectors (PDs) are essential for various health monitoring, night vision, and telecommunications applications, but their detectivity in a wide absorbance region is limited by undesirable electronic response properties. Colloidal quantum dots (CQDs) are a promising system for broad-spectrum detection, whereas their practical potential is hindered by suboptimal dark current characteristics. To overcome these challenges, we propose a layered architecture comprising CQDs and a bulk heterojunction (BHJ) organic film as a hole transport layer. The integration of PbS CQDs offers multiple benefits, including bandgap tuning for minimizing thermal carriers, surface passivation to reduce recombination rates, and the formation of high-quality interfaces with organic layers, which collectively contribute to suppressing dark current leakage and thermal excitations by suppressing stray electrons. By integrating ITIC into the BHJ film, the device detectability is significantly enhanced, reaching 10¹³ Jones in the 400–1000 nm spectral range. This improvement is attributed to the higher lowest unoccupied molecular orbital (LUMO) of ITIC molecules, which effectively hinders electron injection. Additionally, J-aggregation-induced molecular stacking and optimized phase separation of BHJ films contribute to the enhanced performance. The integration of diverse materials offers greater flexibility in device design and functionality, enabling the development of more advanced and sophisticated optoelectronic devices. Furthermore, this approach could significantly enhance the theoretical and practical understanding of optoelectronic device engineering, leading to the development of more advanced optoelectronic devices.

The efficacy of photothermal therapy (PTT) in antitumor applications is often limited by inadequate tumor targeting and low photothermal conversion efficiency (PCE) of photosensitizers. In this study, we designed a photothermal nanoparticle, MPF@IR780, to enhance photosensitizers' targeting and PCE. First, MPF@IR780 improves the delivery of photosensitizers to tumor tissue through the enhanced permeability and retention (EPR) effect. Furthermore, hydrophobic ferrocene was incorporated into the nanoparticle core to increase structural compactness, leading to a strong aggregation-caused quenching (ACQ) effect and an improved PCE of the photosensitizer under near-infrared (NIR) irradiation. Mechanistically, MPF@IR780 induces PANoptosis and ferroptosis in cancer cells through thermal damage and oxidative stress, providing an efficient approach for oncotherapy. This strategy of amplifying the effects of PTT by enhancing the ACQ of photosensitizers offers a promising method for advancing the next generation of PTT.

Metal-organic frameworks (MOFs) are a new class of organic-inorganic hybrid materials that have been widely studied in the past two decades for their potential in catalysis. (1) In this review, we comprehensively summarize the synthesis, application, and potential advancements of MOFs in enzyme immobilization and mimetic enzymes. (2) We also discuss the design principles behind various MOF-based biocatalysts, such as enzyme@MOF composites, and explore their utility in various reactions. (3) Additionally, we highlight the advantages of MOF materials as enzyme mimetics and provide a perspective on potential solutions to current challenges in MOF catalysis. (4) Ultimately, this review provides a general overview of the most recent advances in MOF-based catalyst platforms, including enzyme@MOF biocatalysts and MOF-based nanozymes, in various applications.

Phase separation (PS) plays a fundamental role in organizing aggregates during the viral lifecycle, providing significant opportunities for in viral disease treatment by inhibiting PS. Intrinsically disordered regions (IDRs) have been extensively studied and found to be critical for PS. However, the discovery of small molecules that target residues within IDRs remains underexplored, particularly in the field of pesticides. Herein, we report a novel phytovirucide compound 29, which was screened from a series of vanillin derivatives designed with sulfonylpiperazine motifs. The inactivation efficacy of compound 29 against tomato spotted wilt virus (TSWV) was significantly superior to that of the control agents vanisulfane and ribavirin. Mechanistically, compound 29 binds to the TSWV nucleocapsid protein (NP) at residues Lys68 (K68), Thr92 (T92), and Arg94 (R94), with T92 and R94 located in the IDRs of NP. Mutations at these sites impair the ability to form aggregates. Furthermore, a host factor, GTP (Guanosine Triphosphate)-binding nuclear protein Ran-like (Niben101scf08341g01001, NbRANL), which interacts with NP and promotes its aggregation, was identified. Compound 29 also suppresses the expression of NbRANL, resulting in the dual inhibition of ribonucleoprotein complexes (RNPs) formation. This unique mechanism of action provides insights into IDRs-based virucide discovery.