Chemodynamic therapy (CDT) has shown promising antitumor effects in various malignant tumors. However, its application for glioblastoma (GBM) is significantly hindered by the challenge of delivering CDT agents across the blood-brain barrier (BBB) and achieving efficient tumor targeting. To overcome these obstacles, this study presents a novel DNA nanomachine (Cu@tFNAs-G-A NM) by loading copper ions (Cu²⁺) onto tetrahedral framework nucleic acids (tFNAs) functionalized with dual DNA aptamers. The dual DNA aptamers (GS24 for BBB penetration and AS1411 for tumor targeting) empowered Cu@tFNAs-G-A NM with the ability to effectively penetrate the BBB and selectively accumulate in tumor cells. Upon internalization, the loaded Cu²⁺ reacted with tumor-overexpressed reductive glutathione (GSH) and hydrogen peroxide (H₂O₂), generating hydroxyl radicals (·OH) and inducing tumor cell death. Additionally, Cu@tFNAs-G-A NM was found to be rapidly cleared from the brain and normal tissues within 24 h, minimizing potential systemic toxic side effects. These findings demonstrate the promising potential of Cu@tFNAs-G-A NM for effective CDT against GBM and open up new avenues for the development of targeted therapies for GBM.

Macrocycles are key tools for molecular recognition and self-assembly. However, traditionally prevalent macrocyclic compounds exhibit specific cavities with diameters usually less than 1 nm, limiting their range of applications in supramolecular chemistry. The efficient synthesis of giant macrocycles remains a significant challenge because an increase in the monomer number results in cyclizationentropy loss. In this study, we developed a low-entropy-penalty synthesis strategy for producing giant macrocycles in high yields. In this process, long and rigid monomers possessing two reaction modules were condensed with paraformaldehyde via Friedel–Crafts reaction. A series of giant macrocycles with cavities of sizes ranging from 2.0 to 4.7 nm were successfully synthesized with cyclization yields of up to 72%. Experimental results and theoretical calculations revealed that extending the monomer length rather than increasing the monomer numbers could notably reduce the cyclization-entropy penalty and avoid configuration twists, thereby favoring the formation of giant macrocycles with large cavities. Significantly, the excellent self-assembly capacity of these giant macrocycles promoted their assembly into organogels. The xerogels exhibited enhanced photoluminescence quantum efficiencies of up to 83.1%. Mechanism investigation revealed the excellent assembly capacity originated from the abundant π–π interactions sites of the giant macrocycles. The outstanding emission enhancement resulted from the restricted nonradiative decay processes of rotation/vibration and improved radiative decay process of fluorescence. This study provides an effective and general method for achieving giant macrocycles, thereby expanding the supramolecular toolbox for host–guest chemistry and assembly applications. Moreover, the intriguing assembly and photophysical properties demonstrate the feasibility of developing novel and unique properties by expanding the macrocycle size.

The increased clinical application of cell-based therapies has resulted in a parallel increase in the need for non-invasive imaging-based approaches for cell tracking, often through labeling with nanoparticles. An ideal nanoparticle for such applications must be biologically compatible as well as readily internalized by cells to ensure adequate and stable cell loading. Surface coatings have been used to make nanoparticle trackers suitable for these purposes, but those currently employed tend to have cytotoxic effects. Zwitterionic ligands are known to be biocompatible and antifouling; however, head-to-head evaluation of specific zwitterionic ligands for cell loading has not yet been explored. Magnetic particle imaging (MPI) detects superparamagnetic iron oxide nanoparticles (SPIONs) using time-varying magnetic fields. BecauseMPI can produce high-contrast, real-time images with no tissue depth limitation, it is an ideal candidate for in vivo cell tracking. In this work, we have conjugated hard (permanently charged) and soft (pKa-dependently charged) biomimetic zwitterionic ligands to SPIONs and characterized how these ligands changed SPION physicochemical properties.We have evaluated cellular uptake and subcellular localization between zwitterions, how the improvement in cell uptake generated stronger MPI signal for smaller numbers of cells, and how these cells can be tracked in an animal model with greater sensitivity for longer periods of time. Our best-performing surface coating afforded high cell loading within 4 h, with full signal retention in vivo over 7 days.

The life-threatening colorectal cancer exhibits multilevel immunosuppressive characteristics, including low immunogenicity, abnormal cellular metabolism, and acidic immunosuppressive microenvironment. In this work, multi-synergistic chemotherapeutic drug assemblies are fabricated to activate colorectal cancer immunotherapy by modulating the multilevel immunosuppressive characteristics. Without any drug excipients, the glycolysis inhibitor of lonidamine (LON), indoleamine 2,3-dioxygenase 1 (IDO-1) inhibitor of NLG919 (NLG), and the photosensitizer of chlorine e6 could self-assemble into drug assemblies (LNC) with uniform nano-size distribution and increased drug stability. Moreover, LNC could also promote cellular uptake and enhance drug penetration to enable efficient drug co-delivery. Especially, the photodynamic therapy (PDT) of LNC could disrupt tumor cells to release tumor-associated antigens, thus efficiently suppressing primary tumor growth and improving tumor immunogenicity. Meanwhile, LNC could also reduce the activity of IDO-1 and attenuate the glycolysis metabolism, thereby reversing the multilevel immunosuppressive characteristics to promote T cell activation. Benefiting from the multi-synergistic effects, LNC efficiently eradicates the primary tumor growth and also activates systemic antitumor immunity for metastatic tumor inhibition. Such a simple formulation but a multi-synergistic strategy may accelerate the development of translational nanomedicine for colorectal cancer immunotherapy by using small molecular drug combinations.

Hofmeister effect is a famous physical chemistry phenomenon that was reported a hundred years ago, which firstly refers to the action of certain salts to decrease the solubility of proteins while others increase. The Hofmeister effect on the luminescent properties of cationic organic fluorophore is still obscure, especially for their room temperature phosphorescence (RTP). Herein, hydrophilic groups (quaternization pyridine) were introduced into carbazole molecules to obtain a series of carbazole derivatives (named CZ-Py⁺) with different counter anions in the Hofmeister series. These carbazole derivatives displayed tunable fluorescent color from cyan to yellow in the solid state following the Hofmeister sequence and anti-Hofmeister behavior in an aqueous solution. Moreover, RTP material with tunable emission color and lifetime was achieved by doping CZ-Py⁺ with Hofmeister series anion in polymethyl methacrylate and polyvinyl alcohol, which displayed good performance in time getting information encryption and anti-counterfeiting.

Type I photosensitizers (PSs) with the ability to generate reactive oxygen species (ROS) containing superoxide anion and hydroxyl radical have promising application potential for treating hypoxia tumors, but the deep mechanism of type II ROS converts to the type I ROS in the PSs is still unclear, it is urgent to reveal influencing factors about inducing type I ROS generation. Herein, six PSs with aggregation-induced emission properties, which were fabricated with the same electronic acceptor but different electronic donors and “π-bridge”, have been successfully prepared to explore the influencing mechanism of generating superoxide anion and hydroxyl radical from organic PSs. Experimental results discovered two factors containing molecular structure and aggregated environment could decide the ROS efficiency and types of PSs. On the level of designing molecular structure, we discovered that “π-bridge” with a lower energy level of the lowest triplet state could be beneficial for triggering the production of superoxide anion, and electronic donor of triphenylamine was an important factor in producing hydroxyl radical than another donor of dimethylamine. On the level of designing aggregates of PS-based polymeric nanoparticles, bovine serum albumin could improve largely the generation efficiency of superoxide anion. Due to the satisfactory ROS efficiency and better biocompatibility, synthetic PSs showed excellent photodynamic therapy outcomes in vitro/vivo.

The regulation of emission color, emission efficiency, and asymmetry factor is of great significance for the real applications of circularly polarized luminescent (CPL) materials. Herein, we develop a modular synthetic strategy toward full-color-tunable CPL materials based on chiral macrocyclic aggregation-induced emission (AIE) luminogens via delicate molecular engineering. Modular synthesis of chiral AIEgens with different acceptor moieties has afforded a series of bright solid emitters with tunable emission colors. These chiral cyclic AIEgens have retained high solid-state emission quantum yield and displayed CPL emission from blue to red as nanoaggregates, in liquid crystal matrix and polymer film. The strong acceptor units in the red-emitting chiral AIEgens RBTPE-2CN and SBTPE-2CN have rendered them twisted intramolecular charge transfer properties and solvatochromic luminescence. And polymer matrix with different polarity further facilitates the tuning of CPL emission color from green to red emission. These results have paved a reliable approach toward constructing full-spectra solid-state CPL material.

Cardiac diseases threaten human health and burden the global healthcare system. Cardiomyocytes (CMs) are considered the ideal model for studying the signal transduction and regulation of cardiac systems. Based on the principle of the rhythmical beating process (excitation–contraction coupling mechanism of CMs), investigating the mechanical and electrophysiological signals offered new hope for cardiac disease detection, prevention, and treatment. Considerable technological success has been achieved in electromechanical signal recording. However, most drug assessment platforms attach importance to high-throughput and dynamic monitoring of mechanical or electrical signals while overlooking the measuring principles and physiological significance of the signal. In this review, the development of biosensing platforms for CMs, sensing principles, key measured parameters, measurement accuracy, and limitations are discussed. Additionally, various approaches for the stimulation and measurement of CMs in vitro are discussed to further elucidate the response of these cells to external stimuli. Furthermore, disease modeling and drug screening are used as examples to intuitively demonstrate the contribution of in vitro CM measurement platforms to the biomedical field, thereby further illustrating the challenges and prospects of these sensing platforms.

Cartilage tissue engineering is a promising strategy to repair damaged tissue and reconstruct organ function, but the scaffold-free cartilage regeneration technology is currently limited in its ability to construct three-dimensional (3D) shapes, maintain the chondrogenic phenotype, and express cartilage-specific extracellular matrix (ECM). Recently, cartilaginous organoids (COs), multicellular aggregates with spheroid architecture, have shown great potential in miniaturized cartilage developmental models in vitro. However, high-efficiency and transferable in vivo organoid-based 3D cartilage regeneration technology for preclinical research needs further exploration. In this study, we develop novel cartilaginous organoids bioassembly (COBA) strategy to achieve scaffold-free 3D cartilage regeneration, which displays batch-to-batch efficiency, structural integration, and functional reconstruction. For underlying molecule mechanism, cellular adhesion proteins significantly regulate cell aggregation and cytoskeleton reorganization to form cartilaginous spheroids, and the hypoxic microenvironment created by high-density cell aggregates synergistically activates hypoxia-inducible factor-1α-mediated glycolytic metabolism reprogramming to maintain the chondrogenic phenotype and promote cartilage-specific ECM deposition. Furthermore, separated COs can integrate into a complete and continuous cartilage tissue through the COBA approach, and thus facilitate raising the nasal dorsa in goats after minimally invasive injection. This study thus demonstrates the promise of COBA technology to achieve scaffold-free 3D cartilage regeneration for organoid-based translational applications.

Infectious diseases present significant challenges to global health, thereby extensively affecting both human society and the economy. In recent years, functional probes have demonstrated remarkable potential as crucial biomedical media for the research and treatment of infectious diseases. Their applications in the realm of infectious diseases include pathogen detection, exploration of biological mechanisms, and development of anti-infective drugs. This review provides a concise introduction to the severity, classification, and pathogenesis of infectious diseases. Subsequently, we examined the distinctiveness and design strategies of functional probes for diagnosing and treating infectious diseases, shedding light on their design rationale using typical examples. We discuss the current status and challenges associated with the clinical implementation of functional probes. Furthermore, we explored the prospects of using these probes for the diagnosis and treatment of infectious diseases. This review aims to offer novel insights into the design of diagnostic probes for infectious diseases and broaden their applications in disease treatment.

Nanoparticle surfactants (NPSs) that form via the reversible non-covalent interactions between nanoparticles (NPs) and polymer ligands at the oil-water interface have received great attention in constructing structured liquids with unique stimuli-responsiveness. Introducing dynamic covalent interactions to generate NPSs is expected to achieve a balance between high mechanical strength and dynamic responsiveness of the interfacial assemblies. Here, we present the formation, assembly, and jamming of a new type of NPS by the co-assembly between polydopamine NPs (PDA NPs) and poly(styrene-co-methacrylamidophenylboronic acid) at the oil-water interface. Dynamic covalent boronate ester bonds form in situ at the interface and show multiple responsiveness when applying stimuli such as pH, H₂O₂, and temperature, allowing the controlled assembly/jamming of NPSs and reconfiguration of liquid constructs. Due to the photothermal property of PDA NPs, the temperature responsiveness of boronate ester bonds can also be triggered by irradiating the biphasic system with near-infrared (NIR) light. Moreover, when bringing two droplets encapsulated with NPSs into contact and irradiating the contact area by NIR, thermal welding of droplets can be realized, offering a straightforward to construct droplet networks and modular liquid devices.

The poor prognosis of triple-negative breast cancer (TNBC) results from its high metastasis, whereas inflammation accompanied by excessive reactive oxygen species (ROS) is prone to aggravate tumor metastasis. Although photothermal therapy (PTT) has extremely high therapeutic efficiency, the crafty tumor cells allow an increase in the expression of heat shock proteins (HSPs) to limit its effect, and PTT-induced inflammation is also thought to be a potential trigger for tumor metastasis. Herein, myricetin, iron ions, and polyvinylpyrrolidone were utilized to develop nanomedicines by self-assembly strategy for the treatment of metastatic TNBC. The nanomedicines with marvelous water solubility and dispersion can inhibit glucose transporter 1 and interfere with mitochondrial function to block the energy supply of tumor cells, achieving starvation therapy on TNBC cells. Nanomedicines with excellent photothermal conversion properties allow down-regulating the expression of HSPs to enhance the effect of PTT. Interestingly, the broad spectrum of ROS scavenging ability of nanomedicines successfully attenuates PTT-induced inflammation as well as influences hypoxia-inducible factors-1α/3-phosphoinositide-dependent protein kinase 1 related pathway through glycometabolism inhibition to reduce tumor cell metastasis. Moreover, the nanomedicines have negligible side effects and good clinical application prospects, which provides a valuable paradigm for the treatment of metastatic TNBC through glycometabolism interference, anti-inflammation, starvation, and photothermal synergistic therapy.

Microtubules (MTs) are key players in cell division, migration, and signaling, and they are regarded as important targets for cancer treatment. In this work, two fullerene (C₆₀)-functionalized Ir(III) complexes (Ir-C₆₀1 and Ir-C₆₀2) are rationally designed as dual reactive oxygen species (ROS) regulators and MT-targeted Type I/II photosensitizers. In the dark, Ir-C₆₀1 and Ir-C₆₀2 serve as ROS scavengers to eliminate O₂•^– and •OH, consequently reducing the dark cytotoxicity and reversing dysfunctional T cells. Due to the efficiently populated C₆₀-localized intraligand triplet state, Ir-C₆₀1 and Ir-C₆₀2 can be excited by green light (525 nm) to produce O₂•^– and •OONO^– (Type I) and ¹O₂ (Type II) to overcome tumor hypoxia. Moreover, Ir-C₆₀1 is also able to photooxidize tubulin, consequently interfering with the cellular cytoskeleton structures, inducing immunogenic cell death and inhibiting cell proliferation and migration. Finally, Ir-C₆₀1 exhibits promising photo-immunotherapeutic effects both in vitro and in vivo. In all, we report here the first MT stabilizing photosensitizer performing through Type I/II photodynamic therapy pathways, which provides insights into the rational design of new photo-immunotherapeutic agents targeting specific biomolecules.

The remarkable advantages and promising application potentials of aggregationinduced emission (AIE) materials have seen significant advancements in recent years. Notably, AIE materials incorporating dynamic covalent bonds (DCBs) have garnered escalating attention and demonstrated remarkable progress due to their reversible and self-adaptive properties, thus exhibiting immense potential across various domains including biomedicine, nanomaterials, sensing, and optical displays. This review aims to provide a comprehensive overview of the recent strides in DCBs-based AIE materials, organized by the types of dynamic covalent bonds utilized, such as Diels–Alder reaction, imine bond, transesterification, boronic ester bond, disulfide bond, [2+2] Cycloaddition Reaction and X-yne adducts exchange. Through exemplifying representative cases, we elucidate the design principles of chemical structures and the diverse dynamic behaviors exhibited by DCBs-based AIE materials. Leveraging the principles of dynamic covalent chemistry, these emissive materials can be facilely prepared, and they possess inherent self-adaptability and responsiveness to stimuli. Finally, we present succinct conclusions and discuss future trends in this burgeoning field, offering fresh insights into the design of novel luminescent materials based on dynamic covalent bonds for broader applications.

Introducing fluorescent nanomaterials as artificial antennas of chloroplasts offers a promising approach to enhancing light harvesting in photosynthesis. However, this technology is limited by the dependence of the fluorescence efficiency of nanomaterials on dispersed states that cannot enable nanomaterials inside and outside leaves to play an antenna role. Here, we developed solution and solid dual-state ultra-efficient blue emissive carbon dots (DuB₂-CDs) by regulating the content of graphitic-N, surface hydroxyl groups. and C–Si bonds based on a four-component microwave synthesis. The as-prepared DuB₂-CDs showed intense blue emission in aqueous solution and solid state, with absolute photoluminescence quantum yields of 84.04% and 95.69%, respectively. These features guaranteed that the internal (DuB₂-CDs infiltrating the mesophyll system) and external (DuB₂-CDs remaining on the surface of leaves) artificial antennas can simultaneously enhance the solar energy utilization efficiency of chloroplasts. Compared with the control groups without antenna use and internal antenna use only, the foliar application of DuB₂-CDs substantially enhanced the electron-transport rate, net photosynthesis rate, psbA gene expression, NADPH production, and other plant physiological parameters of living plant during photosynthesis. This work provided a promising strategy for realizing dual-state ultra-efficient emissive CDs while maximizing living plant-photosynthesis augmentation.

Advancements in organic electronics are propelling the development of new material systems, where organic materials stand out for their unique benefits, including tunability and cost-effectiveness. Organic single crystals stand out for their ordered structure and reduced defects, enhancing the understanding of the relationship between structure and performance. Organic cocrystal engineering builds upon these foundations, exploring intermolecular interactions within multicomponent-ordered crystalline materials to combine the inherent advantages of single-component crystals. However, the path to realizing the full potential of organic cocrystals is fraught with challenges, including structural mismatches, unclear cocrystallization mechanisms, and unpredictable property alterations, which complicate the effective cocrystallization between different molecules. To deepen the understanding of this promising area, this review introduces the mechanism of organic cocrystal formation, the various stacking modes, and different growth techniques, and highlights the advancements in cocrystal engineering for multifunctional applications. The goal is to provide comprehensive guidelines for the cocrystal engineering of high-performance molecular materials, thereby expanding the applications of organic cocrystals in the fields of optoelectronics, photothermal energy, and energy storage and conversion.

Molecular aggregation or supramolecular aggregation-induced emission is one of the research hotspots in chemistry, biology, and materials. Herein, we report negatively charged sulfato-β-cyclodextrin (SCD) induced cyanovinylene derivatives (DPy-6C) directional aggregation to form regular nanorods (DPy-6C@SCD) through supramolecular multivalent interactions, not only achieves ultravioletvisible absorption redshifted from 453 to 521 nm but also displays near-infrared (NIR) aggregation-induced emission with a large spectral redshift of 135 nm. The DPy-6C monomer presents random nanosheets with weak fluorescence but obtains regular aggregates after assembly with SCD through electrostatic interactions. In the presence of H⁺, the DPy-6C@SCD can further aggregate into elliptical nanosheets without fluorescence changes due to the protonation of secondary amines. In contrast, the morphology of DPy-6C@SCD becomes flexible and sticks together upon the addition of OH⁻ with an emission blue shift of 72 nm and a 90-fold intensity increase because of disrupting the stacking mode of aggregates, thereby achieving acid-base regulated reversible fluorescence behaviors that cannot be realized by DPy-6C monomer. The DPy-6C@SCD can efficiently select the detection of volatile organic amines both in liquid and gas phases within 5 s at the nanomolar level. Taking advantage of RGB analysis and calculation formula application, the DPy-6C@SCD has been successfully used to monitor various organic amines on a smartphone, accompanied by naked-eye visible photoluminescence. Therefore, the present research provides an efficient directional aggregation method through supramolecular multivalent interactions, which not only realizes topological morphology transformation but also achieves reversible NIR luminescent molecular switch and high sensitivity organic amines fluorescent sensing devices.

Chirality in confined nanospaces has brought some new insights into chirality transfer, amplification, and chiroptical properties. However, chirality switching, which is a common phenomenon in biological systems, has never been realized in confined environments. Herein, we report a type of hexagonal metallacages that shows good host–guest interactions with ethoxy pillar[5]arene and pillar[6]arene, as confirmed by single-crystal X-ray analysis. Importantly, when a chiral pillar[5]arene-based molecular universal joint (MUJ) is used as the guest, the host–guest complexation would drive the alkyl ring of the MUJ flip from outside to inside the cavity of its pillar[5]arene unit, which enables the configuration change along with the chirality inversion of the MUJ. Moreover, the host–guest complexation facilitates the chirality transfer from guests to hosts, giving circularly polarized luminescence to the system. This study provides a unique metallacage-pillararene recognition motif for the chirality switching of planar chiral pillararenes, which will promote the construction of host–guest systems with tunable chirality for advanced applications.

This study presents a novel boron-difluoride complex-based fluorescent nanofilm sensor capable of detecting sarin vapors in the environment by reporting an output fluorescence signal. The sensor’s evaluation demonstrated an exceptionally low detection limit for sarin vapor, even in the presence of various interfering gases, with theoretical and practical limits of detection of 0.7 and 1 ppb, respectively. The sensor featured a rapid response time (less than 2 s), a broad linear detection range (1 ppb–1000 ppm), and superior selectivity for sarin vapor over a group of interfering analytes, outperforming existing sarin sensors. Mechanistic study indicates that the sensor’s heightened sensitivity to sarin vapor is due to the robust affinity of nitrogen atoms within the core BODIQ unit for sarin. Additionally, the tetraphenylethylene structure with steric hindrance effectively inhibits the tight packing of BODIQ derivatives, and forms numerous microporous structures in the self-assembled nanofilm, which are beneficial for the mass transfer, enhancing the sensor efficiency in detecting vapors. Furthermore, we have achieved the differentiation of sarin, diethyl chlorophosphate, and HCl vapor through the analysis of sensing kinetic. This fluorescent sensor opens new avenues for sustainable, low-cost, and environment-friendly portable devices, as well as for environmental monitoring and tracking applications.

Photothermal agents (PTAs) with ultra-high photothermal conversion efficiency (PCE) activated upon near-infrared (NIR) laser irradiation can heat up and destroy tumor cells under low-intensity laser excitation to allow safe and efficient tumor therapy. Herein, an organic PTA with an outstanding PCE of 89.6% is developed from rationally designed perylene diimide (PDI) with electron-donating cyclohexylamine moiety at the bay-positions of its skeleton and chiral phenethylamine (PEA) moiety at its N terminals, termed here PEAPDI. The strong intermolecular interaction between the PDI skeletons induced by PEA together with the intramolecular charge transfer from cyclohexylamine to PDI skeleton severely quenches the fluorescence emission from PEAPDI and significantly enhances its NIR absorption, resulting in super NIR–photothermal conversion. PEAPDI molecules are subsequently encapsulated within silica nanocapsules (SNCs), creating PEAPDI@SNC. Characterized by its small hydrodynamic diameter, monodispersity, high PDI encapsulation efficiency, colloidal stability, and biocompatibility, PEAPDI@SNC exhibits prolonged blood circulation and enhanced permeability and retention effect, enabling targeted accumulation at the tumor site. An in vivo study using a 4T1 tumor–bearing mice model illustrates the agent’s potent tumor ablation capability without side effects at low dosage under NIR laser irradiation (808 nm). The findings demonstrate PEAPDI@SNC’s significant potential as a PTA for tumor treatment.

Several therapeutic drugs including heptamethine cyanine dye (IR-780), doxorubicin (DOX), and others have exhibited positive outcomes in the treatment of multiple myeloma (MM). However, curing MM is still hampered by undesired off-target effects and uncontrolled release of the therapeutics. Herein, we present novel MM-mimicking nanocarriers by integration of DOX, IR-780, and MM cell membrane with zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (D/INPs@CM) for MM treatment. The nanocarriers were fabricated by co-loading DOX and IR-780 into ZIF-8 and further coated with the cell membrane. After intravenous injection, the D/INPs@CM can enter the bone marrow and target the tumor cells owing to bone marrow homing and homologous targeting properties of the MM cell membrane. Once accumulating in the tumor site, ZIF-8 decomposed under the acid microenvironment and released the encapsulated DOX and IR-780. As a result, D/INPs@CM showed the best MM tumor eradication performance compared to D/INPs, without displaying noticeable systemic toxicity. All these features suggest that our biomimetic nanocarriers may have great potential for the precise and targeted therapy of MM and related other hematological malignancies.

Intermolecular charge transfer (inter-CT) is commonly considered to quench luminescence in molecular aggregates, especially for near-infrared (NIR) emission. Herein, by elaborate comparison of π-bridge effects in donor/acceptor (D/A) molecules, it is disclosed that a π-bridge is essential in D/A molecule to involve inter-CT in aggregates for inducing desired thermally activated delayed fluorescence (TADF) and largely suppressing non-radiative decays, and importantly, electrondonating π-bridge is critical to maximize radiative decay for inter-CT dominated emission by effective electronic coupling with bright intramolecular charge transfer (intra-CT) for high-efficiency NIR emission. As a proof-of-concept, TPATAP with thienyl as π-bridge realized prominent photoluminescence quantum yields of 18.9% at 788 nm in solid films, and achieved record-high maximum external quantum efficiencies of 4.53% at 785 nm in devices. These findings provide fresh insight into interplay between inter-CT and intra-CT in molecular aggregates and open a new avenue to attenuate the limitation of energy gap law for developing highly efficient NIR emitters and improving the luminescent efficiency of various inter-CT systems, such as organic photovoltaic, organic long persistent luminescence, etc.

Osteoarthritis (OA) is associated with metabolic imbalance of articular cartilage and an increase of intracellular reactive oxygen species (ROS). Synergistic therapy based on the codelivery of ROS scavengers and antisense oligonucleotides (ASO) into chondrocytes has the potential to effectively treat OA. Here, we developed a novel biocompatible metal-organic framework (MOF)-encapsulated nanozyme/ASO delivery platform (miR/IrO₂@ZIF-8) for OA treatment. IrO₂ nanoparticles with the catalytic activities of superoxide dismutase/catalase were synthesized using a hydrothermal method, resulting in excellent ROS scavenging performance. IrO₂ was further loaded into zeolitic imidazolate framework-8 (ZIF-8) to maintain its catalytic efficacy and regulate its size, surface charge, and biocompatibility to enhance the therapeutic effect of the platform. As an effective ASO delivery carrier, the synthesized IrO₂@ZIF-8 exhibited high antagomiR-181a loading and lysosomal escape capacity, enabling it to rebalance cartilage metabolism. In vitro experiments showed that miR/IrO₂@ZIF-8 could restore ROS levels, mitochondrial membrane potential, and lipid peroxidation in chondrocytes. At the same time, the expression levels of proinflammatory markers (IL-1β, IL-6, and COX-2) as well as the extracellular matrix degrading enzymes (ADAMTS-5 and MMP13) were downregulated, indicating effective antioxidant, anti-inflammatory, and anticartilage degradation effects. Notably, miR/IrO₂@ZIF-8 was able to deliver IrO₂ nanoparticles and antagomiR-181a to the cartilage tissue at a depth of up to 1.5 mm, thus solving the problems of poor permeability and difficult retention of drugs in cartilage tissue. This further improves the synergistic therapeutic effect on OA by inhibiting cartilage degradation. The combination of MOF-encapsulated IrO₂ nanozymes with antagomiR-181a has an excellent therapeutic effect on OA, offering a promising translational medicine paradigm.

Solid bubbles have expanded the SERS assay toolbox, but their detection performance in biofluids is still hampered by the irrational design of the plasmonic sensing interface. A plasmonic bubble aggregate-driven DNA-encoded SERS assay is reported here that enables simultaneous, ultrasensitive, and specific detection of multiple miRNAs in blood samples for accurate cancer diagnosis. In this assay, the buoyancy of plasmonic bubbles allows them to self-aggregate at a droplet apex for SERS reconfiguration, form single-layer bubble aggregates with plasmonic nanogaps, and prevent the coffee ring effect during evaporation assembly. Furthermore, DNA-encoded plasmonic bubbles seamlessly couple with dual-color catalytic hybridization assembly to amplify the specific miRNA-responsive Raman signal, and function as both an analyte concentrator and a Raman signal aggregator without external forces. Using these merits, this magnet-free, portable assay achieves femtomolar dual-miRNA quantitation with single-base resolution, simultaneous miRNA detection across four cell lines, and accurate cancer diagnosis (AUC = 1) via analyzing 40 blood samples with machine learning, thus providing a promising tool for clinical diagnosis.

Photodynamic therapy is a highly recommended alternative treatment for solid tumors, such as cutaneous or luminal tumors, in clinical practice. However, conventional photosensitizers (PSs) often induce undesirable phototoxic effects because of their normal tissue distribution and a reduction in antitumor effects resulting from aggregation-caused quenching effects. The present study developed a novel nanoformulated aggregation-induced emission (AIE)-characteristic PS, nab-TTVPHE, which is composed of human serum albumin as a carrier and TTVPHE as a therapeutic agent, as a more effective cancer treatment with lower phototoxic effects. Notably, the reactive oxygen species generated by TTVPHE were shielded by the nanoaggregate structure, and the photodynamic activity was after nanostructure dissociation. Nab-TTVPHE was actively internalized in tumor cells via secreted protein, acidic and rich in cysteine and released to form nanoaggregates. TTVPHE accumulated in mitochondria, where it triggered mitochondrial damage under light irradiation via its photodynamic activity and induced pyroptosis via the caspase-3/gasdermin E (GSDME) signaling pathway to kill tumor cells. Therefore, this nano-formulated AIE-characteristic PS provides an innovative strategy for cancer treatment with lower phototoxic effect and the ability to boost potential antitumor immunity via GSDME-mediated pyroptosis.

Ultralong thermally activated delayed fluorescence (UTADF) materials play an important role in realizing time-dependent color-tunable afterglow. Some typical carbazole (Cz) derivatives have been reported to exhibit UTADF properties. However, a 10-fold difference in TADF lifetime was found between commercial Cz derivatives and the corresponding lab-synthesized ones, which indicated that UTADF may not be derived from the single Cz derivatives as reported. To reveal the real mechanism, we synthesized three Cz derivatives and one isomer to form three host-guest pairs for optical studies. The photophysical properties revealed that UTADF originated from the intermolecular charge transfer between host and guest, while the ultralong organic phosphorescence was from the guest. Thanks to the rich color variations in luminescence displayed by 4-(1H-benzo[f]indol-1-yl)–4′-(9H-carbazol-9-yl)-[1,1′-biphenyl]–3,3′-dicarbonitrile/4,4′-di(9H-carbazol-9-yl)-[1,1′-biphenyl]–3,3′-dicarbonitrile (CBP-2CN) at different delay times, it can be applied to realize multi-dimensional encryption in both delay time and luminescent color.

To address the unique challenges of diabetic wound healing, wound dressings, particularly multifunctional hydrogels have garnered considerable interest. For the first time, a novel environmentally friendly soy protein-based hydrogel is developed to accelerate the healing of diabetic chronic wounds. Specifically, this hydrogel framework is in direct formation through the dynamic Schiff base between oxidized guar gum and epigallocatechin-3-gallate (EGCG)-modified soy protein isolate. Meantime, the addition of Ag⁺ enhances the cross-linking of the hydrogel network by forming metal-ligand bonds with the catechol groups in EGCG. Interestingly, the stretchability (up to 380%), swelling, and rheology properties of the hydrogel can be controlled by fine-tuning the density of metal-ligand bonds, endowing them with a high potential for precise matching. Additionally, various dynamic bonds endow hydrogel with excellent self-healing ability, adhesiveness, and injectability. This hydrogel also exhibits good antibacterial properties, biocompatibility, and cell migration capabilities. Both in vivo and in vitro experiments demonstrated the outstanding anti-inflammatory capacity of the hydrogel and its ability to modulate macrophage polarization. Consequently, the hydrogel has proven effective in promoting wound healing in a diabetic full-thickness wound model through enhanced angiogenesis and collagen deposition. This eco-friendly plant protein hydrogel offers a sustainable solution for wound care and environmental protection.

The presence of bacterial biofilms and the occurrence of excessive inflammatory response greatly imped the healing process of chronic wounds in diabetic patients. However, effective strategies to simultaneously address these issues are still lacking. Here, a microenvironment-adaptive nanodecoy (GC@Pd) is constructed via the coordination and in situ reduction of palladium ions on gallic acid-modified chitosan (GC) to promote wound healing by synergistic biofilm eradication, inflammation alleviation, and immunoregulation. During the weakly acidic conditions of the biofilm infection stage, GC@Pd serves as a nanodecoy to induce bacterial aggregation. Subsequently, through its oxidase-like activity generating reactive oxygen species and the hyperthermia from photothermal effects, it effectively eliminates the biofilm. As the local microenvironment of diabetic wounds transitions to an alkaline inflammatory state, the enzyme-like activity of GC@Pd adapts to catalase-like activity, effectively eliminating reactive oxygen species at the site of inflammation. Additionally, GC@Pd could selectively capture pro-inflammatory cytokines through Michael addition reactions. In vivo experiments and transcriptomic analysis confirmed that GC@Pd could accelerate the wound transition from inflammatory to proliferative phase by eliminating biofilm infection and reducing the inflammatory response, thus promoting diabetic chronic wound healing. The nanodecoy provides a potential therapeutic strategy for treating biofilm-infected diabetic chronic wounds.

The multifaceted regulation of the chiroptical properties and self-assembly behaviors of chiral fluorescent polymers is of great significance yet remains challenging to achieve. Herein, a series of novel salen-based chiral fluorescent polymers with aggregation-induced emission and varied substitution manners were facilely and efficiently synthesized. Multiple factors were systematically investigated on the chiroptical properties and self-assembly performance of these polymers, which include molecular structures, solvent environments, metal coordination, and liquid crystal (LC) assemblies. Sutle change in the solvent composition can lead to diverse assembly morphologies of all these chiral polymers, from single-handed helical fibers, helical toroids or loops, to spherical structures, consequently leading to an aggregation-reduced circular dichroism (CD) phenomenon. The polymers bearing salen units show highly selective and reversible coordination with Zn²⁺ and can also induce multiple responses in the absorption, luminescence, CD, and circularly polarized luminescence (CPL) of these chiral fluorescent polymers via a coordination- and dissociation-initiated self-assembly tuning. Furthermore, a small amount of the chiral fluorescent polymer in can induce achiral nematic 4-cyano-4′-n-pentylbiphenyl (5CB) to form ordered chiral nematic LC phase with significant improvement in their CD and CPL signal. The absolute absorption and luminescent dissymmetry factors of the resulting supramolecular assemblies can reach the order of 10^-1.

Poly(vinyl alcohol) (PVA) is biodegradable, recyclable, and has high tensile strength. Therefore, it is ideal for the development of environment-friendly sustainable bioplastics. However, at elevated humidity, the mechanical properties of PVA bioplastic films undergo degradation owing to their intrinsic hydrophilic and hygroscopic nature, hindering their applications. This study proposes a nanoconfined assembly strategy to produce humidity-adaptive, mechanically robust, and recyclable bioplastic film. The strong hydrogen bonds between PVA and cellulose nanofibrils inhibit the penetration of water molecules into the film to promote humidity resistance. Further, the robust coordination interactions between bentonite nanoplates, PVA, and cellulose nanofibrils restrict the slip of polymer chains during deformation, leading to enhanced mechanical properties. Benefiting from the nanoconfined assembly architecture in aggregated composites, the resulting reinforced PVA film simultaneously exhibits strength, stiffness, toughness, fracture energy, and tearing energy of 55.9 MPa, 1,275.6 MPa, 162.9 MJ m^-3, 630.9 kJ m^-2, and 465.0 kJ m^-2, respectively. Moreover, the film maintains a strength of approximately 48.7 MPa even at 80% relative humidity for 180 days. This efficient design strategy applies to diverse scales and structured cellulose biomacromolecules. Moreover, it facilitates the application of recyclable high-performance bioplastic films to settings that require high humidity tolerance.

In recent years, the substantial increase in total joint replacements for treating degenerative joint disease has heightened concerns regarding implant loosening and failure. This is especially critical as more young patients are undergoing both initial and subsequent joint replacement procedures. These complications often necessitate additional revision surgeries. Unfortunately, current clinical practices lack effective methods for the early detection of implant failure, and there is a noticeable absence of strategies utilizing molecular markers to identify post-surgery implant issues. This article critically assesses the potential of aggregation-induced emission (AIE) biomarkers in detecting molecular markers relevant to implant failure. It begins by outlining the pathogenesis of implant loosening and identifying pertinent molecular markers. The study then delves into how AIE luminogens (AIEgens) can play a crucial role in detecting processes such as osteogenesis and osteoclastogenesis. Notably, it discusses the utilization of AIEgens in detecting key molecular markers, including TNF-α, osteocalcin, and urinary N-terminal telopeptide. The prospect of AIE biomarkers for the early detection of bone loss and implant failure presents a promising avenue for enhancing our understanding of skeletal health and improving clinical outcomes through timely intervention and personalized treatment approaches. Ongoing research and development in this area are crucial for translating AIE-based technologies into practical tools for optimizing bone health management.

Curved π-electron systems show unique properties and assembly feature that enable the specific applications in materials science and supramolecular chemistry. Herein, fullerene, carbon nanohoop and π-bowl are integrated by the coupling of covalent and supramolecular tactics. Firstly, π-bowl trichalcogenasumanenes (TCSs) are fused with a carbon nanohoop [10]CPP via covalent joint to form molecular crowns 4a/4b, which show structural and electronic complementarity and accordingly strong binding affinity to C₆₀/C₇₀. Secondly, the supramolecular assemblies of 4a/4b with fullerenes afford the host-guest complexes 4a/4b⊃C₆₀/C₇₀ in solution (molar ratio, 2:1) and solid state (molar ratio, 1:1). In the crystals of host–guest complexes, the intra-cluster and inter-cluster interactions are respectively dominated by the [10]CPP and TCSs moieties of 4a/4b. Additionally, it is found that 4a/4b are good photosensitizers for generating ¹O₂ and show structural adaptability in accordance to assembly conditions. 4a/4b take an endo-conformation in their own crystals with TCSs and [10]CPP moieties being bowl-shaped and elliptical, respectively. In contrast, the [10]CPP on 4a/4b changes into circular and the TCSs moiety becomes flat (for 4b) or shows bowl inversion to be exo-conformation (for 4a) in 4a/4b⊃C₆₀/C₇₀.

Phototheranostics has garnered sustained attention due to its significant potential for revolutionizing conventional cancer treatment strategies. While being one of the most commonly employed strategies for constructing phototheranostic systems by engineering the integration of photosensitizers (PSs) into nanosystems, nano- PSs face challenges including complexity in the preparation process, low delivery efficiency, and potential toxicity issues. Contrastingly, the burgeoning popularity of small molecule PSs characterized by aggregation-induced emission (AIE) has become evident in the arena of cancer phototheranostics. This preference is underscored by their well-defined structures, adjustable photophysical properties, and low toxicity. Therefore, acquiring profound insights into the pioneering strides achievable through a solitary small molecule PS with AIE in tumor phototheranostics is of paramount scientific significance. In this review, we will discuss the recent progress of small molecule PSs with AIE properties in cancer diagnosis and phototherapies with representative examples, guided by the ethos of “Complexity made easy”. We also look forward to the future development direction of AIE small molecules, with a central objective of advancing cancer research through a focal emphasis on simplicity, expeditiousness, and safety.