Efficient photosensitizers are crucial for the success of photodynamic therapy (PDT). Herein, we reported two [3+2+1] coordinated organometallic Iridium (III) complexes (labeled as Ir-C1 and Ir-C4). Ir-C1/C4 can generate both type I and type II reactive oxygen species (ROS). In vitro experiments, Ir-C1/C4 show low biotoxicity and high phototoxicity of half-maximal inhibitory concentration values of 14 nM and 33 nM on rectal cancer cell line HCT116, respectively. Western blot analysis revealed that the Ir-C1/C4 activated ferroptosis, apoptosis, and inhibiting autophagy simultaneously. Proteomics analysis demonstrated that the photosensitizers destroyed the endoplasmic reticulum (ER), blocking the signal transmission and material transfer between the ER and other tissues of the cell, especially the ER to Golgi vesicle-mediated transport. Ir-C1/C4 can achieve better antitumor performance than commercial photosensitizer Chlorin e6 and the ferroptosis activator RSL3 at lower concentrations. The low biotoxicity and high phototoxicity make them ideal candidates for PDT. The findings provide new insights into the design of photosensitizers for metal complexes and have significant implications for the development of PDT and related drugs.

Organic light-emitting diodes (OLEDs) based on purely organic room-temperature phosphorescence (RTP) materials often encounter issues of relatively low efficiency and spectral instability. To overcome these limitations, three (arylthio)benzene derivatives (4S, 5S, and 6S) with gradually increased RTP component are designed and compared. Theoretical calculation and photophysical investigation reveal that the fully substituted arylthio effect could enhance the aggregation-induced phosphorescence, enlarge the spin orbital coupling, and reduce the energy gap between S₁ and T₁ as much as possible. As a result, 6S can exhibit single spectra in films with a high phosphorescence efficiency of up to 76.7%, and its doped RTP-OLED furnishes a high maximum external quantum efficiency (EQE) of 15.3% and ultra-stable spectra with the brightness raised from 30 to 2000 cd m⁻². Furthermore, serving 6S as the sensitizer, the RTP-sensitized-fluorescent OLEDs based on fluorescence dopant TBRb and multiple resonance type dopant BN3 both show near three times improvement in electroluminescence performance, with EQE values of 11.3% and 25.6%, respectively. These results demonstrate the feasibility of fully substituted arylthio effect in designing RTP materials and could advance the development of high-performance RTP OLEDs.

Skeletal muscle tissue engineering (SMTE) has recently emerged to address major clinical challenges such as volumetric muscle loss (VML). Here, we report a rotary wet-spinning (RoWS) biofabrication technique for producing human myo-substitutes with biomimetic architectures and functions. Here, we demonstrate how the proposed technique may be used to establish a well-tailored, anisotropic microenvironment that promotes myogenic differentiation of human skeletal muscle–derived pericytes (hPeri). Using high-resolution mass spectrometry–based proteomics with the integration of literature-derived signaling networks, we uncovered that (i) a 3D biomimetic matrix environment (PEG-fibrinogen) confers a less mitogenic microenvironment compared to standard 2D cultures, favoring the formation of contractile-competent bundles of pericyte-derived myotubes in an anchoring-independent 3D state and (ii) the RoWS method promotes an upregulation of muscle matrix structural protein besides increasing contractile machinery proteins with respect to 3D bulk cultures. Finally, in vivo investigations demonstrate that the 3D-biofabricated myo-substitute is fully compatible with the host ablated muscular tissue, exhibiting myo-substitute engraftment and muscle regeneration in a mouse model of VML. Overall, the results show that RoWS offers a superior capability for controlling the myogenic differentiation process on a macroscale and, with future refining, may have the potential to be translated into clinical practice.

A library of rod-like bolapolyphiles with sticky hydrogen-bonded glycerol groups at their ends and having highly branched side chains with a carbosilane-based four-way branching point, all based on the same oligo(phenylene ethynylene) core, has been synthesized and investigated. For these compounds, a A15-type Frank–Kasper phase is formed upon side-chain elongation in the steric frustration range at the transition from the triangular to the much larger square honeycombs. In contrast to the previously known tetrahedral sphere packings the A15 phase is in this case formed by tetrahedral networks of aggregates of parallelly organized π-conjugated rods. This allows the design of compounds with wide ranges of the A15 network down to room temperature. However, its formation becomes strongly disfavored by core fluorination that is attributed to a changing mode of core–core interaction that also modifies the square honeycombs by deformation of the squares into rectangular or rhombic cells, either with or without emergence of tilt of the rods.

Layer-by-layer (LBL) process has emerged as a promising method in the advancement of organic photovoltaics, emphasizing scalability and reproducibility. More importantly, it provides enhanced morphological control for boosting carrier mobility (μ) and power conversion efficiency. By employing a multiscale approach that combined first-principles calculations, molecular dynamics simulations, and kinetic Monte Carlo methods, the relationship between LBL morphology engineering and carrier mobility in donor/acceptor (PM6/L8-BO) thin films is elucidated. During solvent evaporation, the order of solid-phase formation in LBL films was top surface, bottom region, and then the middle region. The early solid precipitation from precursor solutions was acceptor, resulting in a well-ordered molecular arrangement and reducing energy disorder of acceptor LUMO levels. Furthermore, the difference in energy disorders between the A/D blend region and the pure A or D domains enabled LBL morphology engineering to balance electron and hole mobilities, thereby mitigating charge accumulation and recombination. LBL-manufactured films presented higher carrier mobility ({\mu }_{\text{e}}^{\text{LBL}}={\mu }_{\text{h}}^{\text{LBL}}=1.9\times {10}^{-3} cm² V⁻¹ s⁻¹) compared to bulk heterojunction (BHJ) films ({\mu }_{\text{e}}^{\text{BHJ}}>{\mu }_{\text{h}}^{\text{BHJ}}=0.1\times {10}^{-3} cm²·V⁻¹ s⁻¹). These mechanisms provided insights into strategies for enhancing charge extraction of photo-generated charge carriers through LBL engineering, driving the development of efficient organic photovoltaic materials.

To improve the long-term therapeutic efficacy of colorectal cancer, we propose a synergistic treatment strategy involving dual-pathway, multistep induction of long-term hyperimmunity combined with photothermal-chemotherapy. To implement this strategy, infinite coordination polymer nanoparticles (SN38-Mn(II)-EGCG ICP NPs) were prepared by coordinating SN38, EGCG, and Mn²⁺. These nanoparticles were then coated with polydopamine (PDA) and grafted with folate-PEG-thiol (FA-PEG-SH) onto their surfaces, producing tumor-targeting folate-modified PDA infinite coordination polymer nanocomposites (ICP@FA-PDA nanocomposites). These nanocomposites exhibit a particle size of 94.9 ± 1.6 nm with a high drug loading capacity (83.3% ± 1.5%), drug release under acidic conditions while maintaining stability in physiological environments. Furthermore, each component within the nanocomposites serves multiple functions. Notably, the incorporation of multiple components triggers a powerful antitumor immune effect and establishes enduring immune memory through a dual-pathway and multistep approach, which is produced with the activation of the cGAS-STING pathway and immunogenic cell death (ICD) by a four-component multistep process. Under a low-dose regimen, this approach induces dual-pathway hyperimmunity effect and generates ultra-long immunological memory, marked by a ninefold increase in CD8⁺ T cell infiltration, a fourfold increase in CD4⁺ T lymphocytes, a fourfold reduction in Treg cells, and a fivefold increase in memory T cells. The remarkable therapy efficacy is achieved by hyperimmunity effect combination of SN38 and EGCG chemotherapy and photothermal therapy. In vivo studies demonstrated that mice treated with ICP@FA-PDA nanocomposites achieved complete eradication of cancer within 21 days, with no recurrence observed within 60 days. These nanocomposites hold significant promise and potential for future clinical translation.

The repair and functional reconstruction of bone defects resulting from trauma, surgical resection, degenerative diseases, and congenital malformations are major clinical challenges. Bone tissue engineering has significant advantages in the treatment of severe bone defects. Vascularized bone repair scaffolds are gradually attracting attention and development because of their excellent biomimetic properties and efficient repair efficiency. Three-dimensional (3D) printing technology, which can be used to fabricate structures at different scales using a wide range of materials, has been used in the production of vascularized bone repair scaffolds. This review discusses the research progress in 3D printing for vascularized bone repair scaffolds. Angiogenesis-osteogenesis coupling in the bone regeneration process is first introduced, followed by a summary of the 3D printing technologies, printing inks, and bioactive factors used to fabricate vascularized bone repair scaffolds. Notably, this review focuses on structural design strategies for vascularized bone repair scaffolds. Finally, the application of vascularized bone repair scaffolds in medicine, as well as challenges and outlooks for future development, are described.

Tumor metastasis accounts for the major portion of cancer-related deaths. Magnetic resonance imaging (MRI) is a valuable imaging modality for tumor diagnosis in clinical applications, offering detailed soft tissue images with excellent spatial resolution and good biosafety. However, the low sensitivity and the lack of specificity to disease sites limit the application of MRI contrast agents in early and precise detection of small primary and metastatic cancers. Therefore, there is an urgent need for innovative MRI contrast agents with enhanced relaxivity, target ability, and pharmacokinetics to improve imaging sensitivity and widen the detection window in the meantime. Here, we reported a dual-targeting protein MRI contrast agent (EPR-DTPA-Gd) fused by a nanobody against epidermal growth factor receptor 1 (EGFR), integrin α_vβ₃-binding cyclic nonapeptide, and elastin-like polypeptide. We found that this protein contrast agent exhibited high sensitivity and specificity for the tumor overexpressed EGFR and integrin α_vβ₃ in MRI. Furthermore, EPR-DTPA-Gd had high longitudinal relaxation rate (r₁) (68.76 mM⁻¹ s⁻¹ per molecule) and an improved pharmacokinetics behavior for tumor imaging. Using T1-weighted imaging, EPR-DTPA-Gd successfully detected a series of early metastases with the smallest 0.012 mm² (213 µm × 58 µm) in a liver metastasis model of human cervical carcinoma HeLa cells, which cannot be detected by the clinically approved T1-weighted contrast agent. The heightened detection sensitivity intrinsic to EPR-DTPA-Gd facilitates precise imaging of tumor lesions, supporting sophisticated image-guided interventions and early management in high-risk patient cohorts.

Dental caries represents one of the most widespread oral bacterial infections, affecting billions of individuals worldwide and presenting significant public health challenges. Effective diagnosis and treatment are hindered by the limitations of traditional clinical treatment methodologies, which often involve laborious examinations and invasive procedures. In this study, we employ an aggregation-induced emission probe, MeOTpy, for instant molecular detection and photodynamic treatment of dental caries. MeOTpy interacts specifically with cariogenic bacteria, exhibiting bright fluorescence upon binding to bacteria and generating reactive oxygen species under white light irradiation. This aggregation-induced photosensitivity enables rapid assessment of carious disease through fluorescent detection in dental plaque samples, facilitating easy identification of lesion sites in decayed teeth treated with MeOTpy. Furthermore, photodynamic inhibition of cariogenic biofilms is achieved by culturing ex vivo biofilms isolated from children with severe early childhood caries. MeOTpy also effectively prevents dental caries while preserving oral microbial diversity in a cariogenic infection model on rat pups. This study presents an integrated strategy for the precise diagnosis and treatment of dental caries at the point of care.

Postoperative pain and tumor recurrence are critical challenges following malignant tumor resection. To address these issues, we developed a supramolecular gel delivery system loaded with ropivacaine microcrystals (RopC Gel). Using PEG400 as the solvent, we successfully screened and identified matrix materials capable of forming supramolecular hydrogels through a heating–cooling process. By strategically leveraging the hydrophilic and hydrophobic properties of the gel matrix, we controlled its mechanical strength and degradation rate by adjusting the ratio of hydrophilic to hydrophobic components, resulting in a degradable, injectable, and self-healing gel delivery system. In both rat plantar incision and mouse tumor resection pain models, RopC Gel provided long-lasting analgesia for up to 5 days. Notably, tumor-resected mice treated with RopC Gel demonstrated extended survival and slower tumor progression. Further in vitro and in vivo experiments revealed that RopC Gel affects mitochondrial function by promoting the accumulation of reactive oxygen species in tumor cells, inducing pyroptosis, stimulating immunogenic cell death (ICD), and activating anti-tumor immune responses. This work offers an innovative solution for postoperative tumor resection management. Additionally, the controllable degradation properties outlined in this study provide an efficient strategy for the controlled release of multiple drugs, with the potential for widespread clinical applications.

The aberrant behavior of lipid droplets (LDs) is often indicative of cellular dysfunction, which may contribute to the development of a range of diseases, particularly metabolic dysfunction-associated steatotic liver disease (MASLD) and atherosclerosis (AS). Consequently, there is an urgent need to develop fluorescence probes targeting LDs to monitor the progression of disease. In this study, an unanticipated one-pot boron tribromide (BBr₃)/boron trichloride (BCl₃)-promoted cyclization reaction was discovered, yielding a bromo-/chloro-substituted triphenylamine (TPA) derivative (TPA-Br/TPA-Cl). TPA-Br was successfully transformed into new TPA-containing donor-acceptor (D–A) molecules which show typical aggregation induced emission (AIE) property. Among these new AIE emitters, TPA-N shows the most promising LDs targeting specificity, lowest toxicity and best photo-stability. Ex vivo studies further demonstrate that TPA-N can be used to fluorescence image fatty liver and AS plaque quickly and effectively.

Colorectal cancer (CRC) screening and early diagnosis is an effective strategy for reducing CRC mortality. However, the current detection methods involve exorbitant costs and complex procedures, which are inconvenient for large-scale screening. Given its high prevalence in malignant tissues and feces of CRC patients, Fusobacterium nucleatum (F. nucleatum) has emerged as a crucial biomarker for the early detection of CRC. Herein, we propose an F. nucleatum-specific recognition strategy for CRC screening and diagnosis. A novel nanobioprobe (AIE-Pep) with aggregation-induced emission (AIE) characteristics was synthesized by conjugating a red/near-infrared (NIR) emissive AIE luminogen (AIEgen) with a FadA-targeting peptide (ASANWTIQYND). The robust binding affinity between the peptide and FadA on F. nucleatum allows AIE-Pep NPs to adhere selectively to F. nucleatum, and emits strong red/NIR fluorescence. In the model of the orthotopic CRC, AIE-Pep NPs can precisely localize F. nucleatum around CRC. Moreover, AIE-Pep NPs demonstrated a limit of detection (LOD) of 82.97 CFU/mL for F. nucleatum, which could significantly differentiate the feces of CRC mice from those of normal mice. Overall, this study presents a pivotal approach to specifically identifying F. nucleatum and holds immense potential for CRC diagnosis.

In the last decade, the rise of antibiotic resistance has heightened interest in antimicrobial peptides and lipopeptides as promising alternatives to conventional antibiotics because of their lower propensity to develop resistance. However, lipopeptides often show undesired cytotoxicity due to their non-selective membrane disruptive effect, and their limited aqueous solubility represents a matter of concern from a pharmaceutical point of view. This study demonstrates a panel of ultrashort cationic lipopeptides (USCLs) consisting of a tetrapeptide (L1), originated from buforin II, coupled with saturated fatty acids of different lengths. Our results highlight that the 16-carbon fatty acid lipopeptide (Pal-L1) exhibits relevant antibacterial activity against multiresistant Staphylococcus aureus strain. However, the formation of heterogenic aggregates in cell culture medium and toxic effects on human cells were also observed. Pal-L1 formulation with the randomly methylated α-cyclodextrin (RAMEA) and the sulfobutylether-β-cyclodextrin (SBECD) has resulted in a production of ultralow-sized molecular dispersion systems and reduced lipopeptide toxicity without compromising its antimicrobial activity. With titration ¹H-NMR, 2D NMR experiments, together with molecular dynamics simulations, we described the size, structure, stoichiometry, and dissociation constant of the supramolecular complexes. Interactions of neutral and negatively charged model liposomes with Pal-L1 lipopeptide in the presence or absence of cyclodextrins serve an explanation for the membrane selectivity, and based on the results, we proposed a potential mechanism of action for the Pal-L1+cyclodextrin complexes on different biological membranes. Overall, our model characterization points out that cyclodextrin formulation improves the therapeutical applicability of lipopeptides.

Compared to fluorescence imaging, chemiluminescence imaging does not need external excitation light, and hence presents high imaging depth and signal-to-noise ratio without autofluorescence and phototoxicity, making it a promising tool for biological detection and analysis. However, the target-specific activatable near-infrared emission chemiluminescent probes still need to be developed for the precise diagnosis of diseases. In this paper, we synthesized four direct near-infrared emission Schaap's chemiluminophores (AINCL, AIFCL, ABTCL, and APYCL) by incorporating different electronic acceptors, respectively, and studied the effect of the acceptors on the optical properties of the chemiluminophores. To achieve the specific detection of hydrogen sulfide (H₂S)-related diseases, we used H₂S-cleavable 2,4-dinitrophenylsulfonate to cage the phenol groups in the chemiluminophores. It was demonstrated that the endogenous H₂S in inflammations and tumors could activate effectively the chemiluminescence with high specificity, which provided the precise location of nidus in chemiluminescence imaging and allowed us to perform surgical resection.

Human papillomavirus (HPV) is a highly prevalent venereal pathogen accounting for genital warts and various cancers like cervical, anal, and oropharyngeal cancers. Although imiquimod, a topical medication, is commonly used to treat genital warts induced by HPV, its potential as an in situ immune response regulator for HPV-related cancers has rarely been explored. In this study, we developed an innovative synergistic therapeutic platform by integrating near-infrared-II (NIR-II) absorbing aggregation-induced emission (AIE) agent (TPE-BT-BBTD) and imiquimod into an injectable hydrogel named TIH. TPE-BT-BBTD molecule that serves as a photothermal agent, with exposure to a 1064 nm laser, effectively destroys tumor cells and releases tumor-related antigens. During the thermogenesis process, the hydrogel melts and releases imiquimod. The released imiquimod, in conjunction with the dead tumor antigens, stimulates dendritic cell maturation, activating the immune system to ultimately eliminate residual cancer cells. This novel approach combines the immunomodulatory effects of imiquimod with a 1064 nm-excitable photothermal agent in a hydrogel delivery system, offering a promising tactic for combating HPV-associated cancers.

Urogenital system tumors include prostate cancer, bladder cancer, ovarian cancer, and other very common solid tumor diseases with high morbidity and high mortality. The unique physiological and anatomical features of the urogenital system render it particularly amenable to the application of tissue imaging techniques for diagnostic purposes. The advancement of aggregation-induced emission (AIE) materials has addressed the limitations associated with conventional fluorescent materials that are prone to aggregation-caused quenching. This advancement has facilitated the development of innovative AIE fluorescent materials characterized by enhanced photostability, an increased signal-to-noise ratio, and improved imaging quality. This article reviews the research progress of AIE biosensors in the diagnosis of urogenital tumors. It mainly involves biomarker diagnostic in vitro and fluorescence imaging in urogenital solid tumors such as prostate cancer, uterine cancer, bladder cancer, and ovarian cancer, which are based on AIE biosensors. In addition, a comprehensive description of AIE biosensors’ synthesis and application strategies is provided. This includes a detailed elucidation of in vitro diagnostic platforms and intracellular imaging mechanisms based on the basic principles of AIE, accompanied by a presentation of quantitative analysis and cell imaging results. In addition, the limitations, challenges and suggestions of AIE biosensors application in the field of tumor diagnosis are summarized, and the development prospect of AIE biosensors in the field of tumor diagnosis is prospected. This article reviews the application of AIE biosensors in the diagnosis of urogenital tumors, and also provides a catalyst for exploring the characteristics of AIE biosensors and its wide application in the field of disease diagnosis.

Electronic excited state in molecular aggregate or exciton states continue to attract great attention due to the increasing demands for applications of molecular optoelectronics and sensing technology. The working principle behind the application is closely related to the excited state structure and dynamic processes in molecular aggregate. In our previous review article (Aggregate 2021; 2: e91), we focused more on the molecular mechanism for aggregation-induced emission process. Here, we are going to summarize our recent progress on theoretical investigations on the effects of excitonic coupling (J) and the intermolecular charge transfer (CT) on the excited state structure and dynamic processes. These are in general missing for molecular quantum chemistry studies. We will first present a novel definition of exciton coherence length which can present a bijective relation with the radiative decay rate and obviously we have clarified the confusion appeared in literature. Then, we will look at the CT effect for aggregate starting from a simple three-state model coupled with quantum chemical calculation for molecular dimer and we focus on the intensity borrowing, which can turn H-aggregate into emissive when the electron transfer and hole transfer integrals possessing the same sign and being large enough. We are able to propose a molecular descriptor to design molecular materials possibly possessing both high photoluminescence quantum yield and carrier mobility. Finally, we introduce our work on the modified energy gap law for non-radiative decay rate in aggregates. We found there exist optimal J to minimize the non-radiative decay loss.

Polymer deformation spans 7–10 orders of magnitude in length scales, making its analysis a significant challenge. Optical force probes (OFPs), functional molecular motifs in polymer mechanochemistry, enable the study of mechanical properties by undergoing force-activated optical changes, such as absorption, fluorescence, or chemiluminescence. This review highlights OFPs integrated within polymer materials, focusing on their mechanical properties, optical methods for force elucidation, and the insights they provide. Special attention is given to high-resolution microscopy combined with OFPs, enabling qualitative and quantitative imaging of material damage and failure at unprecedented spatial resolution. While binary OFPs respond at critical strain thresholds, ideal for detecting permanent damage and stress hotspots, continuum OFPs track strain proportionally through reversible optical mechanisms, providing dynamic, real-time strain mapping. Together, these systems advance material diagnostics, offering complementary capabilities to study stress distribution, improve durability predictions, and understand polymer failure mechanisms.