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A biocompatible probe PGA-BFA is rationally designed and developed by a simple co-assembly of γ-PGA with BHQ3-RVRRGFF-AIE. PGA-BFA can help image high furin-expression cancer cells and tiny tumors in a fluorescence “turn-on” manner.

Total phenolic content (TPC), phenolic profiles, and antioxidant activity of free and bound extracts of Sargassum polycystum, obtained by different extraction solvents and hydrolysis methods, were investigated. Aqueous acetone afforded the highest free TPC and antioxidant ability, followed by aqueous ethanol and aqueous methanol. Twelve free phenolic compounds were identified by ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS), including two hydroxycinnamic acids, seven flavonoids, one stilbene, and two phlorotannins. Three to nine different free phenolic compounds were extracted by these solvents with different compositions, including nine by 70% acetone and eight by 70% methanol, 70% ethanol, and 50% ethanol. The highest total content of free phenolic compounds determined by high-performance liquid chromatography-diode array detection was obtained from 70% ethanol. Alkaline hydrolysis afforded higher bound TPC (274.27 mg GAE/100 g DW) and antioxidant ability than acid hydrolysis. Five bound phenolic compounds were characterized by UHPLC-MS and five were released from alkaline hydrolysis, whereas two were released from acid hydrolysis. Total content of bound phenolic compounds released by alkaline hydrolysis was 14.68-fold higher than that by acid hydrolysis. The free and bound TPC, phenolic profiles, and antioxidant activities depended on the extraction solvent used. These results indicate that S. polycystum is a potentially useful antioxidant source and contribute to the development of seaweed-based functional foods. PRACTICAL APPLICATION: Phenolics are usually divided into free and bound forms based on their extractability and interaction with cell wall components. The nutritional effects of bound phenolics in algae have long been neglected. These topics contribute to the development of seaweed-based functional foods.

Dendritic cell (DC)-derived small extracellular vesicles (DEVs) are recognized as a highly promising alternative to DC vaccines; however, the clinical testing of DEV-based immunotherapy has shown limited therapeutic efficacy. Herein, we develop a straightforward strategy in which DCs serve as a cell reactor to exocytose high-efficient DEV-mimicking aggregation-induced emission (AIE) nanoparticles (DEV-AIE NPs) at a scaled-up yield for synergistic photodynamic immunotherapy. Exocytosed DEV-AIE NPs inherit not only the immune-modulation proteins from parental DCs, enabling T cell activation, but also the loaded AIE-photosensitizer MBPN-TCyP, inducing superior immunogenic cell death (ICD) by selectively accumulating in the mitochondria of tumor cells. Eventually, DEV-AIE synergistic photodynamic immunotherapy elicits dramatic immune responses and efficient eradication of primary tumors, distant tumors, and tumor metastases. In addition, cancer stem cells (CSCs) in 4T1 and CT26 solid tumors were significantly inhibited by the immune functional DEV-AIE NPs. Our work presents a facile method for the cellular generation of EV-biomimetic NPs and demonstrates that the integration of DEVs and AIE photosensitizers is a powerful direction for the production of clinical anticancer nanovaccines.

Focused oxidative stress of the specific organelles (e.g., endoplasmic reticulum (ER) and mitochondrion) of cancer cells can boost the immunogenic cell death (ICD) effect for cancer immunotherapy. Herein, an ER-targeted bioprobe with aggregation-induced emission (AIE) characteristics (TPE-PR-FFKDEL) was rationally designed and synthesized by integrating a new AIE photosensitizer with ER targeting peptide, which has been demonstrated to be able to efficiently induce ER oxidative stress to evoke ICD. Compared with the photosensitizer hypericin that is well-known as an ER-targeted ICD inducer, TPE-PR-FFKDEL can lead to more robust emission of immunostimulatory damage-associated molecular patterns such as surface-exposed cal-reticulin, ATP secretion, and high-mobility group protein B1 (HMGB1) and heat shock protein 70 (HSP 70) expression. Furthermore, a range of immune responses are activated to protect mice from the attack of cancer cells in vivo.

Supramolecular nanomaterials as drug carriers have recently received increasing attention due to their intrinsic merits such as high stability, strong inclusion capability, and facile modification of the parental structure; however, intelligent ones with combined capacities of long blood circulation, highly efficient tumor cell uptake, and site-oriented drug release inside tumor cells are still rather limited. Herein, we report a strategy using supramolecular aggregation-induced emission (AIE) nanodots for image-guided drug delivery, which integrate both the advantages of AIE and supramolecular nanomaterials. The supramolecular AIE dots are prepared by the host-guest coassembly of the matrix metalloproteinase-2 (MMP-2) sensitive PEG-peptide (PEG2000-RRRRRRRR (R8)-PLGLAG-EKEKEKEKEKEK (EK6)) and functional α-cyclodextrins (α-CD) derivatives that are conjugated with the anticancer drug gemcitabine (GEM) and a far-red/near-infrared fluorescent rhodanine-3-acetic acid-based AIE luminogen, respectively. The supramolecular AIE dots realize long blood circulation time by virtue of the zwitterionic stealth peptide EK6. After largely accumulating in tumor tissues by the enhanced permeability and retention effect, the supramolecular AIE dots can successively respond to the tumor-overexpressed MMP-2 and intracellular reductive microenvironment, achieving both enhanced cancer cellular uptake and selective GEM release within cancer cells, which thus exhibit excellent tumor inhibition ability in both subcutaneous and orthotopic pancreatic tumor models.

Special attention has been paid to the organic afterglow materials (OAM) for their fascinating properties. However, poor stability at air and complicated structure design hinder the development of OAM. Herein, sol-gel, a facile and simple technique, is employed to synthesize a series of organic/inorganic hybrid nanocomposites (N1/SiO2, N2/SiO2, and N3/SiO2) by covalently linking three common aryl imides with crosslinked silica skeleton. These nanomaterials show excitation wavelength-dependent and colorful (yellow, red and green) afterglow of organic imides with long lifetime up to 1.1 s at air. Interestingly, the ultralong phosphorescence is ultrastable under various conditions: water, high temperature, UV irradiation and in vivo, due to the protection of inorganic silica. In particularly, heating to 500 °C does not quench the afterglow of organic luminophore in nanocomposites, but forms new ultralong phosphorescence originated from space-conjugation of silica and carbonyl. The afterglow nanomaterials display huge advantages in the applications of advanced anti-counterfeiting and bioimaging.

Extracellular vesicles (EVs) released by mesenchymal stem cells (MSCs) have exhibited regenerative capability in animal models of ischemia-reperfusion (I/R) acute kidney injury (AKI) and are considered as potential alternatives to direct MSC therapy. However, real-time in vivo imaging of MSC-EVs in renal I/R injury has yet to be established. Renal intracellular targets of MSC-EVs responsible for their regenerative effects also remain elusive. Here, we report that we real-time observed MSC-EVs specifically accumulated in the injured kidney and were taken up by renal proximal tubular epithelia cells (TECs) via DPA-SCP with aggregation-induced emission (AIE) characteristics. DPA-SCP precisely tracked the fate of MSC-EVs in a renal I/R injury mouse model for 72 h and exhibited superior spatiotemporal resolution and tracking ability to popular commercially available EV tracker PKH26. Further analysis revealed that the accumulated MSC-EVs stimulated mitochondrial antioxidant defense and ATP production via activating the Keap1-Nrf2 signaling pathway, which protected TECs against oxidative insult by reducing mitochondrial fragmentation, normalizing mitochondrial membrane potential, and increasing mitochondrial DNA copy number. Increased microRNA-200a-3p expression in renal TECs induced by MSC-EVs was identified as a regulatory mechanism contributing to the protective actions on mitochondria as well as stimulating the renal signal transduction pathways. In conclusion, MSC-EVs accumulated in the renal tubules during renal I/R injury and promoted the recovery of kidney function via activating the Keap1-Nrf2 signaling pathway and enhancing mitochondrial function of TECs. DPA-SCP with AIE characteristics allows noninvasive and precise in vivo visualization of MSC-EVs in kidney repair.

Near-infrared (NIR) fluorescent probes can deeply penetrate through tissues with little damage. To facilitate image-guided theranostics, researchers usually apply a desired amount of photosensitizers to achieve effective photothermal responses. However, these probes could easily suffer from low photostability and aggregated-caused quenching effect in high concentrations. In this paper, the rational incorporation of an aggregated-induced emission (AIE) unit into the structure of heptamethine cyanine IR-780 is reported. Using tetraphenylethene (TPE) as an AIE core, we synthesize three TPE-modified IR-780 probes (IR-780 AIEgens) via different linkages. The IR-780 derivatives all show enhanced AIE features, in which the probe with an ether linkage (IR780-O-TPE) is superior in rapid cell uptake, high targeting capacity, and good photostability. Moreover, IR780-O-TPE exhibits the strongest cytotoxicity to HeLa cells (IC50 = 3.3 μM). The three IR-780 derivatives displayed a photothermal response in a concentration-dependent manner, in which IR-780 AIEgens are more cytotoxic than IR-780, with IC50 of 0.3 μM under 808 nm laser irradiation. In tumor-bearing mice, the optimal probe IR780-O-TPE also showed a more effective photothermal response than IR-780. By illustrating the relationship between aggregation state with photophysical properties, cell imaging, and cytotoxicity, this work is helpful in modulating NIR-based photosensitizers into AIE features for efficient image-guided theranostics.

Understanding the mechanism and progression of neutrophil-involved diseases (e.g., acute inflammation) is of great importance. However, current available analytical methods neither achieve the real-time monitoring nor provide dynamic information during the pathological processes. Herein, a peroxynitrite (ONOO

Seaweeds are widely known superfood in coasts where most anthropogenic heavy metal discharges are inputted and stored. The present study analyzed 11 seaweed species and 13 heavy metals to test the hypothesis that the species-specific capacity of heavy metal bioaccumulation had great significance to health risk of human. The seaweeds were collected from tropic coasts of Hainan Island. We comparatively determined the bioaccumulation level of metals in different species. The results revealed that the red algae mainly concentrated V, Se, Mn, Ni, and Ag. The brown algae mainly concentrated Cr, Co, Cu, Cd, As and Fe, while the green algae mainly concentrated Zn and Pb. The cluster analysis, principal component analysis and metal pollution index indicated that Padina crassa, Sargassum thunbergii, Caulerpa racemosa and Asparagopsis taxiformis showed similar metal bioaccumulation behavior. The health risk assessment revealed that the overall hazard index (HI) of seaweeds consumption to adults was less than 1, while the HI of Sargassum oligocystum, Turbinaria ornate, Sargassum polycystum and Sargassum thunbergii consumption to children was greater than 1, suggesting a moderate or high risk to children. Moreover, the exposure amount and the carcinogenic risk parameter indicated that As and Cr were the limiting factor for seaweeds consumption. Overall, our findings here largely supported our hypothesis that the heavy metal bioaccumulation behavior and health risk was highly variable and complex among different species. We thus suggested that the species-specific health risk of heavy metals in seaweeds should be cautiously evaluated in natural environments.

Ultrasonic-assisted extraction (UAE) coupled with deep eutectic solvent (DES) is a novel, efficient and green extraction method for phytochemicals. In this study, the effects of 16 DESs coupled with UAE on the extraction rate of polyphenols from Paederia scandens (Lour.) Merr. (P. scandens), an edible and medicinal herb, were investigated. DES synthesised with choline chloride and ethylene glycol at a 1:2 M ratio resulted in the highest extractability. Moreover, the effects of extraction parameters were investigated by using a two-level factorial experiment followed by response surface methodology The optimal parameters (water content in DES of 49.2%, the actual ultrasonic power of 72.4 W, and ultrasonic time of 9.7 min) resulted in the optimal total flavonoid content (TFC) (27.04 mg CE/g DW), ferric-reducing antioxidant power (FRAP) value (373.27 μmol Fe(Ⅱ)E/g DW) and 2,2'-azino-bis(3-ethylbenzthiazoline)-6-sulfonic acid radical (ABTS

The selective identification and removal of senescent cells including senescent cancer cells are very important to prolong life and improve the treatment efficacy of cancer therapy. In this study, we integrated the high selectivity of enzyme-instructed self-assembly (EISA) and efficient reactive oxygen species (ROS) generating property of a novel luminogen with aggregation-induced emission (AIE) character to selectively identify and remove senescent HeLa (s-HeLa) cells. The s-HeLa cells expressed high levels of β-galactosidase (β-Gal), which led to the selective accumulation and formation of nanomaterials of Comp. 1 in the cells. Upon white light irradiation, the nanomaterials efficiently produced ROS and therefore killed s-HeLa cells. Our study demonstrated a promising strategy to selectively remove senescent cells and improve the treatment efficacy of cancer therapy.

In recent years, organic/polymer photothermal nanoagents including semiconducting polymer nanoparticles and small-molecule organic photothermal agents-encapsulated nanoparticles have attracted large attention from researchers in the biomedical field, owing to their excellent optical properties, good biocompatibility, easy processability, and flexible surface functionalization, as well as their combined functions of photoacoustic (PA) imaging and photothermal therapy (PTT). In this review, we summarize the recent advances in organic/polymer photothermal nanoagents for in vivo PA imaging and PTT applications. In particular, we focus on the design strategies, which are composed of traditional approaches and emerging mechanisms, especially based on “intramolecular motion-induced photothermy” strategy to regulate the photophysical properties of organic/polymer photothermal nanoagents for boosted in vivo PA imaging and PTT.

Extracellular vesicles (EVs) attract much attention in liver pathology because they regulate cell-cell communication and many pathophysiological events by transferring their cargos. Monitoring and understanding the in vivo fate and therapeutic capacity of these EVs is critical for the development and optimization of EV-based diagnosis and therapy. Herein, we demonstrate the use of an aggregation-induced emission luminogen, DPA-SCP, for the real-time tracking of EVs derived from human placenta-derived mesenchymal stem cells (MSCs) and their therapeutic effects in a mouse acute liver injury (ALI) model. In vitro, DPA-SCP does not alter the inherent characteristics of MSC-derived EVs and shows extremely low toxicity. Moreover, DPA-SCP exhibited superior labeling efficiency and tracking capability to the most popular commercial EV trackers, PKH26 and DiI. In vivo, DPA-SCP precisely and quantitatively tracked the behaviors of EVs for 7 days in the mouse ALI model without influencing their regenerative capacity and therapeutic efficacy. The therapeutic effects of EVs may attribute to their ability for reducing inflammatory cell infiltration, enhancing cell survival and antiapoptotic effects. In conclusion, DPA-SCP with an AIE signature serves as a favorable and safe tracker for in vivo real-time imaging of EVs in liver regeneration.

Due to the aggregation-caused quenching (ACQ) and weak photo-penetrating ability, the application of phototheranostic agents in drug delivery field is greatly limited. Ferroptosis, a newly discovered cell death mode, has not been extensively studied in the field of phototherapy up to now. Here, a new near-infrared II (NIR-II) molecule with aggregation-induced emission (AIE) property (named TSST) co-assembled with DHA-PEG and ferrocene as nanoparticles (DFT-NP), which was rationally designed and synthesized. The DFT-NP exhibited enhanced NIR-II fluorescence, photothermal, photoacoustic, magnetic resonance imaging, AIE and ferroptosis capacities. The NIR-II fluorescence intensity of obtained nanoparticles was improved, owing to the strong interaction between DHA and TSST, which limited the intramolecular rotation restriction and non-radiative attenuation of TSST to discourage energy dissipation in aggregation state. Inspiringly, the generated photothermal effect by DFT-NP can promote the Fenton reaction of ferrocene and H

Organic near-infrared room temperature phosphorescence (RTP) materials have unparalleled advantages in bioimaging due to their excellent penetrability. However, limited by the energy gap law, organic matters with long wavelengths (> 700 nm) and long lifetimes (> 100 ms) have not been reported so far. In this work, we have obtained organic RTP materials with long wavelengths (657–732 nm) and long lifetimes (102–324 ms) for the first time through the one-axis two-wing guest-host strategy. The one axis refers to that the guest molecule has sufficient conjugation to reduce the lowest triplet energy level and the two wings refer to that the host assists the guest in exciton transfer and inhibits the non-radiative transition of guest excitons. These materials exhibit good tissue penetration in bioimaging. Thanks to the characteristic of long lifetime and long wavelength emissive RTP materials, the tumor imaging in living mice with a signal to background ratio value as high as 43 is successfully realized. This work provides a practical solution for the construction of organic RTP materials with both long wavelengths and long lifetimes.

Photoacoustic (PA) imaging emerges as a promising technique for biomedical applications. The development of new strategies to boost PA conversion without depressing other properties (e.g., fluorescence) is highly desirable for multifunctional imaging but difficult to realize. Here, we report a new phenomenon that active intramolecular motions could promote PA signal by specifically increasing thermal-to-acoustic conversion efficiency. The compound with intense intramolecular motion exhibits amplified PA signal by elevating thermal-to-acoustic conversion, and the fluorescence also increases due to aggregation-induced emission signature. The simultaneously high PA and fluorescence brightness of TPA-TQ3 NPs enable precise image-guided surgery. The preoperative fluorescence and PA imaging are capable of locating orthotopic breast tumor in a high-contrast manner, and the intraoperative fluorescence imaging delineates tiny residual tumors. This study highlights a new design guideline of intramolecular motion amplifying PA effect.

In this work, we have obtained organic room temperature phosphorescence/RTP materials with long wavelengths (657-732 nm) and long lifetimes (102-324 ms) for the first time through the one-axis two-wing guest-host strategy. The one axis refers to that the guest molecule has sufficient conjugation to reduce the lowest triplet energy level and the two wings refer to that the host assists the guest in exciton transfer and inhibits the non-radiative transition of guest excitons. These materials exhibit good tissue penetration in bioimaging. Thanks to the characteristic of long lifetime and long wavelength emissive RTP materials, the tumor imaging in living mice with a signal to background ratio value as high as 43 is successfully realized. This work provides a practical solution for the construction of organic RTP materials with both long wavelengths and long lifetimes used in bioimaging.

Aggregation-induced emission luminogens (AIEgens) hold promise for biomedical imaging and new approaches facilitating their aggregation state are desirable for fluorescence enhancement. Herein, a series of surfactant-stripped AIEgen micelles (SSAMs) with improved fluorescence are developed by a low-temperature surfactant-stripping method to encapsulate AIEgens in temperature-sensitive Pluronic block copolymer. After stripping excessive surfactant, SSAMs exhibit altered optical properties and significantly higher fluorescence quantum yield. Using this method, a library of highly concentrated fluorescent nanoparticles are generated with tunable absorption and emission wavelengths, permitting imaging of deep tissues at different wavelengths. SSAMs remain physiologically stable and can pass safely through gastrointestinal tract (GI) without degradation in the harsh conditions, allowing for fluorescence and photoacoustic imaging of intestine with high resolution. d-amino acids (DAA), a natural metabolite for bacteria, can be chemically conjugated on the surface of SSAMs, enabling non-invasive monitoring of the microbial behavior of ex vivo fluorescently labeled gut microbiota in the GI tract.

Pure organic persistent room temperature phosphorescence (RTP) materials have attracted wide attention owing to their great potential in various applications, particularly in bioimaging. However, it is still a challenge to manufacture organic RTP materials possessing quite high efficiency and long lifetime, owing to the high requirements for triplet excitons. In this study, a series of keto derivatives with efficient RTP in crystals are developed through the regulation of molecular aggregation states by simple alkyl groups, resulting in impressive luminescence performance with a longer lifetime and higher efficiency of up to 868 ms and 51.59%, respectively. All the alkyl-substituted derivatives exhibit bright RTP intensities after heavy grinding with a pestle, indicating their robust RTP features, which are suitable for many fields. Encouraged by the excellent RTP performance of these luminogens in the crystalline state, successful orthotopic lung tumor imaging with a high signal-to-background ratio (SBR) of 65 is demonstrated in this study to provide the promise of pure organic RTP materials for disease diagnosis, which hold the advantages of low autofluorescence interference and high signal-to-background ratio.

The study of purely organic room-temperature phosphorescence (RTP) has drawn increasing attention because of its considerable theoretical research and practical application value. Currently, organic RTP materials with both high efficiency (ФP > 20%) and a long lifetime (τP > 10 s) in air are still scarce due to the lack of related design guidance. Here, we report a new strategy to increase the phosphorescence performance of organic materials by integrating the RTP host and RTP guest in one doping system to form a triplet exciplex. With these materials, the high-contrast labelling of tumours in living mice and encrypted patterns in thermal printing are both successfully realized for the first time by taking advantage of both the long afterglow time (up to 25 min in aqueous media) and high phosphorescence efficiency (43%).

Persistent room temperature phosphorescence (p-RTP) of pure organic compounds is drawing much attention due to its unique advantages and promising applications in anticounterfeiting, encryption, bioimaging, etc. Achieving efficient p-RTP, however, remains challenging. In this contribution, we designed and synthesized three benzoic acid–carbazole conjugates, 4-BACZ, 3-BACZ and 2-BACZ, with strong hydrogen bonding and a dimer structure in their crystals. Compared with their ester counterparts, whose highest RTP efficiency (Φp) is 2.6%, these acids exhibit significantly boosted Φp of 6.9%, 3.4% and 2.6% for 4-BACZ, 3-BACZ and 2-BACZ, respectively. Such enhancement should be ascribed to the effective and abundant hydrogen bonding in the crystals, which significantly depressed the vibrational dissipation. This effect is also confirmed by the theoretically calculated much lower reorganization energies. These crystals are also readily fabricated into biocompatible nanoparticles (NPs) with an inherited p-RTP characteristic. Such a p-RTP feature of the crystals and the NPs makes them highly promising for versatile applications. Herein, the application of these materials in anticounterfeiting and high resolution in vivo afterglow bioimaging is demonstrated.

Despite of the enthusiastic research in aggregation-induced emission luminogens (AIEgens) in recent years, the ones that can be smoothly used for sophisticated biomedical applications such as in vivo bioimaging of pulmonary metastatic tumors during surgery are still limited. Herein, we report the design and synthesis of a new series of far-red/near-infrared (FR/NIR) fluorescent AIEgens that consist of methoxy-substituted tetraphenylethene (TPE) as the electron-donating moiety, (1,3-dimethyl)barbituric acid as the electron-withdrawing moiety, and different π-bridge units. As compared to benzene or 3,4-ethylenedioxythiophene, using thiophene as the π-conjugation unit between the donor and acceptor results in a relatively higher absolute fluorescence quantum yield (14.5 %) in water when formulating the corresponding AIEgens into nanoparticles (AIE dots) with an amphiphilic co-polymer as the doping matrix. The highly FR/NIR-emissive thiophene-based AIE dots are demonstrated to be potent for intraoperative detection of pulmonary metastatic tumors, particularly the micro-sized ones, with excellent signal-to-background ratio.

Fluorescent probes capable of precise detection of atherosclerosis (AS) at an early stage and fast assessment of anti-AS drugs in animal level are particularly valuable. Herein, a highly bright aggregation-induced emission (AIE) nanoprobe is introduced by regulating the substituent of rhodanine for early detection of atherosclerotic plaque and screening of anti-AS drugs in a precise, sensitive, and rapid manner. With dicyanomethylene-substituted rhodanine as the electron-withdrawing unit, the AIE luminogen named TPE-T-RCN shows the highest molar extinction coefficient, the largest photoluminescence quantum yield, and the most redshifted absorption/emission spectra simultaneously as compared to the control compounds. The nanoprobes are obtained with an amphiphilic copolymer as the matrix encapsulating TPE-T-RCN molecules, which are further surface functionalized with anti-CD47 antibody for specifically binding to CD47 overexpressed in AS plaques. Such nanoprobes allow efficient recognition of AS plaques at different stages in apolipoprotein E-deficient (apoE

Both fluorescence and photoactivity activatable probes are particularly valuable for cancer theranostics as they allow for sensitive fluorescence diagnosis and on-demand photodynamic therapy (PDT) against targeted cancer cells at the same time, which undoubtedly promote the diagnostic accuracy and reduce the side effects on normal tissues/cells. Here, we show that enzyme-instructed self-assembly (EISA) is an ideal strategy to develop a both fluorescence and reactive oxygen species (ROS) generation capability activatable probe with aggregation-induced emission (AIE) signature. As a proof-of-concept, we design and synthesize a precursor TPE-Py-FpYGpYGpY that consists of an AIE luminogen (TPE-Py) and a short peptide with three tyrosine phosphates (pY), which permits selective fluorescence visualization and PDT of alkaline phosphatase (ALP)-overexpressed cancer cells. TPE-Py-FpYGpYGpY has good aqueous solubility thanks to the hydrophilic phosphotyrosine residues and hence leads to weak fluorescence and negligible ROS generation ability. After ALP enzymatic dephosphorylation of the precursors, however, self-assembly of ALP-catalysed products occurs and the resultant nanostructures are activated to be highly emissive and efficiently produce ROS. Cellular studies reveal that TPE-Py-FpYGpYGpY is capable of differentiating cancer cells and normal cells, specifically pinpointing and suppressing ALP-overexpressed cancer cells. This study may inspire new insights into the design of advanced activatable molecular probes.

The study of purely organic room-temperature phosphorescence (RTP) has drawn increasing attention because of its considerable theoretical research and practical application value. Currently, organic RTP materials with both high efficiency (ΦP > 20%) and a long lifetime (τP > 10 s) in air are still scarce due to the lack of related design guidance. Here, a new strategy to increase the phosphorescence performance of organic materials by integrating the RTP host and RTP guest in one doping system to form a triplet exciplex, is reported. With these materials, the high-contrast labeling of tumors in living mice and encrypted patterns in thermal printing are both successfully realized by taking advantage of both the long afterglow time (up to 25 min in aqueous media) and high phosphorescence efficiency (43%).

Osteoporosis is a skeletal metabolic disease characterized by reduced bone mass and a high susceptibility to fractures, in which osteoblasts and osteoclasts are highly involved in the abnormal bone remodeling processes. Recently, low‑magnitude, high‑frequency whole‑body vibration has been demonstrated to significantly reduce osteopenia experimentally and clinically. However, the underlying mechanism regarding how osteoblastic activity is altered when bone tissues adapt to mechanical vibration remains elusive. The current study systematically investigated the effect and potential molecular signaling mechanisms in mediating the effects of mechanical vibration (0.5 gn, 45 Hz) on primary osteoblasts in vitro. The results of the present study demonstrated that low‑level mechanical stimulation promoted osteoblastic proliferation and extracellular matrix mineralization. In addition, it was also revealed that mechanical vibration induced improved cytoskeleton arrangement in primary osteoblasts. Furthermore, mechanical vibration resulted in significantly increased gene expression of alkaline phosphatase, bone morphogenetic protein 2 and osteoprotegerin, and suppressed sclerostin gene expression, as determined by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analyses. Mechanical vibration was observed to upregulate gene and protein expression levels of osteogenesis‑associated biomarkers, including osteocalcin and Runt‑related transcription factor 2. In addition, RT‑qPCR and western blotting analysis demonstrated that mechanical vibration promoted gene and protein expression of canonical Wnt signaling genes, including Wnt3a, low‑density lipoprotein receptor‑related protein 6 and β‑catenin. In conclusion, the present study demonstrated that mechanical vibration stimulates osteoblastic activities and may function through a potential canonical Wnt signaling‑associated mechanism. These findings provided novel information that improves the understanding of the molecular mechanisms involved in osteoblastic activities in response to mechanical vibration, which may facilitate the scientific application of mechanical vibration for the treatment of osteoporosis in the clinic.

Oxygen deficiency is the main obstacle of hypoxia-related theranostics, thus this is a considerable amount of research focusing on the development of methods to supply oxygen by taking advantage of hypoxia-responsive properties of nanoparticles. However, strategies to properly penetrate hypoxic regions by the nanoparticles remains an unmet challenge. In this work, a biomimetic nanozyme capable of possessing catalase-like activity and the efficient direct penetration of hypoxic areas in tumor tissues was developed to supply oxygen based on catalytic tumor microenvironment-responsive reaction, providing substantial tumor hypoxia relief with nearly 3-fold reduction compared to untreated tumor tissues. To demonstrate the advantages of the nanozymes in overcoming hypoxia, a theranostic nanosystem model composed of the core/shell nanozymes and aggregation-induced emission (AIE) molecules was designed. The nanosystem was able to present multi-modal imaging of tumors and modulated the tumor microenvironment for improved photodynamic therapy (PDT) by cascade reactions of therapeutic effector molecules, thereby providing significantly enhanced therapeutic benefits in inhibiting tumor growth and lung metastasis of orthotopic breast cancer. This conceptual study showed the multifaceted features of biomimetic nanozymes as tumor therapeutics and demonstrated the encouraging potential for modulating hypoxia as an application for tumor theranostics.

Pure organic persistent room-temperature phosphorescence (p-RTP) under ambient conditions is attractive but challenging due to the slow intersystem crossing process and susceptibility of triplet excitons. Fabrication of pure organic RTP luminogens with simultaneously high efficiency and ultralong lifetime still remains a daunting job, owing to their conflicting requirements for the T1 nature of (n,π*) and (π,π*) characteristics, respectively. Herein, a group of amide-based derivatives with efficient p-RTP is developed through the incorporation of spin-orbital-coupling-promoting groups of carbonyl and aromatic π units, giving impressive p-RTP with lifetime and efficiency of up to 710.6 ms and 10.2%, respectively. Furthermore, two of the luminogens demonstrate intense p-RTP after vigorous mechanical stimulation, indicating their robust nature, which is rarely encountered. Efficient and robust p-RTP even in the amorphous state endows them promising potential for encryption and bioimaging with facile fabrication processes. A bioimaging study with live mice indicates that such highly robust p-RTP is tremendously beneficial for in vivo afterglow imaging with an ultrahigh signal-to-background ratio of 428. These results strongly imply the possibility of realizing efficient and robust p-RTP from pure organics even without meticulous protection, thus paving the way to their promising and versatile applications.