Regulating Triplet Excitons of Organic Luminophores for Promoted Bioimaging.

Afterglow materials with organic room temperature phosphorescence (RTP) or thermally activated delayed fluorescence (TADF) exhibit significant potential in biological imaging due to their long lifetime. By utilizing time-resolved technology, interference from biological tissue fluorescence can be mitigated, enabling high signal-- to-background ratio imaging. Despite the continued emergence of individual reports on RTP or TADF in recent years, comprehensive reviews addressing these two materials are rare. Therefore, this review aims to provide a comprehensive overview of several typical molecular designs for organic RTP and TADF materials. It also explores the primary methods through which triplet excitons resist quenching by water and oxygen. Furthermore, we analyze the principal challenges faced by afterglow materials and discuss key directions for future research with the hope of inspiring developments in afterglow imaging.

Multi-Responsive Afterglows from Aqueous Processable Amorphous Polysaccharide Films.

Polymer-based room-temperature phosphorescence (RTP) materials, especially polysaccharide-based RTP materials, earn sustained attention in the fields of anti-counterfeiting, data encryption, and optoelectronics owing to their green regeneration, flexibility, and transparency. However, those with both ultralong phosphorescence lifetime and excitation wavelength-dependent afterglow are rarely reported. Herein, a kind of amorphous RTP material with ultralong lifetime of up to 2.52 s is fabricated by covalently bonding sodium alginate (SA) with arylboronic acid in the aqueous phase. The resulting polymer film exhibits distinguished RTP performance with excitation-dependent emissions from cyan to green. Specifically, by co-doping with other fluorescent dyes, further regulation of the afterglow color from cyan to yellowish-green and near-white can be achieved through triplet-to-singlet Förster resonance energy transfer. In addition, the water-sensitive properties of hydrogen bonds endow the RTP property of SA-based materials with water/heat-responsive characteristics. On account of the color-tunable and stimuli-responsive afterglows, these smart materials are successfully applied in data encryption and anti-counterfeiting.

Chaihu Shugan San ameliorated cognitive deficits through regulating gut microbiota in senescence-accelerated mouse prone 8.

Background: Traditional Chinese medicines exhibit promising preventive effects on Alzheimer's disease. Chaihu Shugan San (CSS) is a well-known traditional herbal formula whose several kinds of ingredients have the potential of ameliorating Alzheimer's disease. The present study aimed to evaluate the effects of CSS on the microbiota-gut-brain axis and cognitive deficits of senescence-accelerated mouse prone 8 (SAMP8) mice as well as investigate the underlying mechanisms. Methods: Thirty 5-month-old SAMP8 mice were randomly divided into the model group (SAMP8), CSS low-dose treatment group (CSSL), and CSS high-dose treatment group (CSSH). Ten SAMR1 mice were used as the normal control, and ten SAMP8 mice treated with donepezil were used as the positive control of cognitive function. CSS was orally administrated to SAMP8 mice for 8 weeks. The Morris water maze test was used to evaluate cognitive function. Histological staining was used to observe neuronal injury and Aß deposition. Transmission electron microscopy was used to observe the synaptic ultrastructure. 16S rRNA gene analysis was performed to measure the changes in intestinal microbiota. Results: The results showed that CSS significantly improved the learning function and memory deficits of aged SAMP8 mice in the Morris water maze examination. CSS ameliorated neuronal injury, synaptic injuries, and Aß deposition in the brain of SAMP8 mice. In addition, CSS also significantly improved microbiota composition in terms of elevating Lactobacillus reuteri and decreasing Staphylococcus xylosus in the feces of aged SAMP8 mice. Conclusion: These findings suggested that CSS might have a preventive potential for cognitive deficits in aging through regulating gut microbiota, which paved the way for the application of CSS for prevention and therapeutic purposes for mild cognitive impairment as well as Alzheimer's disease.

Highly bright aggregation-induced emission nanodots for precise photoacoustic/NIR-II fluorescence imaging-guided resection of neuroendocrine neoplasms and sentinel lymph nodes.

Owing to the complementary high spatial resolution and signal-to-noise ratio, the dual-modality imaging technique of photoacoustic imaging (PAI)/the second near-infrared window fluorescence imaging (NIR-II FI) holds great promise for the detection of tumor tissues and sentinel lymph nodes (SLNs). Herein, by developing two aggregation-induced emission luminogens (AIEgens) (C-NTBD and O-NTBD) with benzodithiadiazole as the electron acceptor, PAI/NIR-II FI was applied to the diagnosis and treatment of neuroendocrine neoplasms (NENs) and their SLNs for the first time. Both AIEgens exhibited good PAI properties as well as intense NIR-II fluorescence emission. Among them, C-NTBD nanoparticles (NPs) have better PAI and NIR-II FI performance with maximum absorption at 732 nm and emission peak at 1042 nm. In NENs-bearing nude mice model, after successful preoperative localization of NENs by PAI, NIR-II FI was then used to detect SLNs. Under the NIR-II FI guidance of C-NTBD NPs, an SLN with a diameter of 1 mm located in the chest wall and far away from the primary tumor site was even detected and precisely removed. This dual-modality imaging technology could improve the detection of NENs and the accuracy of intraoperative SLNs dissection, improve patient prognosis, and provide a new strategy for the precise treatment of NENs.

An Activatable Near-Infrared Afterglow Theranostic Prodrug with Self-Sustainable Magnification Effect of Immunogenic Cell Death.

Herein, we report an activatable near-infrared (NIR) afterglow theranostic prodrug that circumvents high background noise interference caused by external light excitation. The prodrug can release hydroxycamptothecin (HCPT) in response to the high intratumoral peroxynitrite level associated with immunogenic cell death (ICD), and synchronously activate afterglow signal to monitor the drug release process and cold-to-hot tumor transformation. The prodrug itself is an ICD inducer achieved by photodynamic therapy (PDT). PDT initiates ICD and recruits first-arrived neutrophils to secrete peroxynitrite to trigger HCPT release. Intriguingly, we demonstrate that HCPT can significantly amplify PDT-mediated ICD process. The prodrug thus shows a self-sustainable ICD magnification effect by establishing an "ICD-HCPT release-amplified ICD" cycling loop. In vivo studies demonstrate that the prodrug can eradicate existing tumors and prevent further tumor recurrence through antitumor immune response.

Near-infrared aggregation-induced emission nanodots for early diagnosis of tongue squamous cell carcinoma and sentinel lymph node mapping.

Fluorescence imaging has been widely used in the biomedical field owing to its merits of high sensitivity, excellent accuracy, high biosafety, etc. However, despite the good performance of fluorescent materials in the diagnosis of subcutaneous tumors or some orthotopic tumors in mice, their potential clinical application for most orthotopic tumors in humans is still limited due to their weak tissue penetration ability and the high thickness of human tissues. Given that the human tongue can extend out of the mouth and is approximately 1 cm thick, the diagnosis of tongue squamous cell carcinoma (TSCC) by fluorescence has great potential for clinical applications. However, to the best of our knowledge, a few studies have been performed to detect tongue tumors using fluorescence imaging, and most of them are administered in a subcutaneous tumor-bearing mouse model and are based on fluorescent materials with aggregation-caused quenching effects. Herein, by developing DPA-TPE-DCM with intense near-infrared fluorescence emission in the aggregation state, aggregation-induced emission materials were used for the first time in the early diagnosis of orthotopic TSCC and sentinel lymph node (SLN) mapping in an immunocompetent mouse model of orthotopic TSCC with a high signal-to-background ratio of 10.2. Moreover, with the guidance of the fluorescence of DPA-TPE-DCM NPs, SLNs smaller than 2 mm in diameter were successfully excised. This study provides new insight and a method for the early diagnosis of TSCC in clinical practice and provides more possibilities to broaden the potential clinical applications of fluorescent materials.

Amplification of Activated Near-Infrared Afterglow Luminescence by Introducing Twisted Molecular Geometry for Understanding Neutrophil-Involved Diseases.

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-) and environmental pH dual-responsive afterglow luminescent nanoprobe is designed and synthesized. In the presence of ONOO- at physiological pH, the nanoprobes show activated near-infrared afterglow luminescence, whose intensity and lasting time can be highly enhanced by introducing the aggregation-induced emission (AIE) effect with a twisted molecular geometry into the system. In vivo studies using three diseased animal models demonstrate that the nanoprobes can sensitively reveal the development process of acute skin inflammation including infiltration of first arrived neutrophils and acidification initiating time, make a fast and accurate discrimination between allergy and inflammation, and rapidly screen the antitumor drugs capable of inducing immunogenic cell death. This work provides an alternative approach and advanced probes permitting precise disease monitoring in real time.

Activatable Persistent Luminescence from Porphyrin Derivatives and Supramolecular Probes with Imaging-Modality Transformable Characteristics for Improved Biological Applications.

Persistent luminescence without excitation light and tissue autofluorescence interference holds great promise for biological applications, but is limited by available materials with long-wavelength emission and excellent clinical potential. Here, we report that porphyrin derivatives can emit near-infrared persistent luminescence over 60 min after cessation of excitation light or on interaction with peroxynitrite. A plausible mechanism of the successive oxidation of vinylene bonds was demonstrated. A supramolecular probe with a ß-sheet structure was constructed to enhance the tumor targeting ability and the photoacoustic and persistent luminescence signals. Such probes featuring light-triggered function transformation from photoacoustic imaging to persistent luminescence imaging permit advanced image-guided cancer surgery. Furthermore, peroxynitrite-activated persistent luminescence of the supramolecular probe also enables rapid and precise screening of immunogenic cell death drugs.

A wearable AIEgen-based lateral flow test strip for rapid detection of SARS-CoV-2 RBD protein and N protein.

Accurate and rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is significant for early tracing, isolation, and treatment of infected individuals, which will efficiently prevent large-scale transmission of coronavirus disease 2019 (COVID-19). Here, two kinds of test strips for receptor binding domain (RBD) and N antigens of SARS-CoV-2 are established with high sensitivity and specificity, in which AIE luminogens (AIEgens) are utilized as reporters. Because of the high brightness and resistance to quenching in aqueous solution, the limit of detection can be as low as 6.9 ng/mL for RBD protein and 7.2 ng/mL for N protein. As an antigen collector, an N95 mask equipped with a test strip with an excellent enrichment effect would efficiently simplify the sampling procedures. Compared with a test strip based on Au nanoparticles or fluorescein isothiocyanate (FITC), the AIEgen-based test strip shows high anti-interference capacity in complex biosamples. Therefore, an AIEgen-based test strip assay could be built as a promising platform for emergency use during the pandemic.

Boosting Photoacoustic Effect via Intramolecular Motions Amplifying Thermal-to-Acoustic Conversion Efficiency for Adaptive Image-Guided Cancer Surgery.

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.

Root Canal Disinfection Using Highly Effective Aggregation-Induced Emission Photosensitizer.

Root canal (RC) therapy is the primary treatment of dental-pulp and periapical diseases. The mechanical method and chemical irrigation have limitations in RC therapy. Much attention has focused on exploring more controllable and efficacious antimicrobial methods. Although the introduction of photodynamic therapy (PDT) has provided the ideas for RC debridement, the problems of low photosensitive efficiency and nonsignificant germicidal potency of traditional photosensitizers (e.g., methylene blue) have not been solved. Since the concept of "aggregation-induced emission" (AIE) was proposed, optimization of photosensitizers has been boosted considerably. Herein, an AIE photosensitizer, DPA-SCP, with a strong ability to generate singlet oxygen, is proposed for use as an antibacterial application in infected RCs. The antimicrobial activity of DPA-SCP against Enterococcus faecalis suspensions was tested. To explore the antibacterial ability of this photosensitizer against bacterial-biofilm colonization on the inner walls of RCs, we established a model of bacterial biofilm infection. PDT mediated by DPA-SCP had a significant germicidal effect on E. faecalis suspensions and 21-day biofilms in human RCs. PDT mediated by DPA-SCP could achieve efficiency equivalent to that observed using 1% NaOCl, and lead to no significant change in the dentin surface, chemical corrosion, or cytotoxicity.

A peptide-based aggregation-induced emission bioprobe for selective detection and photodynamic killing of Gram-negative bacteria.

Herein, we report a new bioprobe with aggregation-induced emission (AIE) characteristics by conjugation of a far-red/near-infrared emissive AIE luminogen and two polymyxinB peptides. Due to the strong binding effect between polymyxin B and the lipopolysaccharide in the cell wall of Gram-negative bacteria, the bioprobe can selectively visualize Gram-negative bacteria and effectively kill them via photodynamic treatment.

Polymeric Nitric Oxide Delivery Nanoplatforms for Treating Cancer, Cardiovascular Diseases, and Infection.

The shortened Abstract is as follows: Therapeutic gas nitric oxide (NO) has demonstrated the unique advances in biomedical applications due to its prominent role in regulating physiological/pathophysiological activities in terms of vasodilation, angiogenesis, chemosensitizing effect, and bactericidal effect. However, it is challenging to deliver NO, due to its short half-life (<5 s) and short diffusion distances (20-160 µm). To address these, various polymeric NO delivery nanoplatforms (PNODNPs) have been developed for cancer therapy, antimicrobial and cardiovascular therapeutics, because of the important advantages of polymeric delivery nanoplatforms in terms of controlled release of therapeutics and the extremely versatile nature. This reviews highlights the recent significant advances made in PNODNPs for NO storing and targeting delivery. The ideal and unique criteria that are required for PNODNPs for treating cancer, cardiovascular diseases and infection, respectively, are summarized. Hopefully, effective storage and targeted delivery of NO in a controlled manner using PNODNPs could pave the way for NO-sensitized synergistic therapy in clinical practice for treating the leading death-causing diseases.

HCPT-peptide prodrug with tumor microenvironment -responsive morphology transformable characteristic for boosted bladder tumor chemotherapy.

As a common method for postoperative adjuvant treatments of bladder tumor, chemotherapy encounters low tumor targeting, short tumor retention time and bad bioavailability in clinical applications, which result in unsatisfactory high chemotherapeutical doses, frequent administration and subsequent severe side effects. Herein, we innovatively introduced the enzyme-assisted assembly to construct a bladder tumor-specific transformable peptide prodrug (i.e. HCPT-FF-GFLG-EEYSA). The prodrug targeted bladder tumor through the specific binding capacity of YSA to EphA2 and underwent on-demand structural transformation intracellularly from micelles to fibrils catalyzed by cathepsin B (CtsB), of which EphA2 and CtsB are overexpressed on the outer membrane and in cytoplasm of bladder tumor cells, respectively. Comparing with hydroxycamptothecin (HCPT), the prodrug can prolong the drug retention time and release the active drug in a sustained manner, which in turn decrease the administration frequencies of chemotherapeutics and reduce the side toxicities, etc. This strategy provides an alternative for bladder tumor chemotherapeutics and shows great potential to inhibit the relapse of postoperative tumors.

Planar and Twisted Molecular Structure Leads to the High Brightness of Semiconducting Polymer Nanoparticles for NIR-IIa Fluorescence Imaging.

Semiconducting polymer nanoparticles (SPNs) emitting in the second near-infrared window (NIR-II, 1000-1700 nm) are promising materials for deep-tissue optical imaging in mammals, but the brightness is far from satisfactory. Herein, we developed a molecular design strategy to boost the brightness of NIR-II SPNs: structure planarization and twisting. By integration of the strong absorption coefficient inherited from planar π-conjugated units and high solid-state quantum yield (ΦPL) from twisted motifs into one polymer, a rise in brightness was obtained. The resulting pNIR-4 with both twisted and planar structure displayed improved ΦPL and absorption when compared to the planar polymer pNIR-1 and the twisted polymer pNIR-2. Given the emission tail extending into the NIR-IIa region (1300-1400 nm) of the pNIR-4 nanoparticles, NIR-IIa fluorescence imaging of blood vessels with enhanced clarity was observed. Moreover, a pH-responsive poly(ß-amino ester) made pNIR-4 specifically accumulate at tumor sites, allowing NIR-IIa fluorescence image-guided cancer precision resection. This study provides a molecular design strategy for developing highly bright fluorophores.

Regulating the Photophysical Property of Organic/Polymer Optical Agents for Promoted Cancer Phototheranostics.

On the basis of the Jablonski diagram, the photophysical properties of optical agents are highly associated with biomedical function and efficacy. Herein, the focus is on organic/polymer optical agents and the recent progress in the main strategies for regulating their photophysical properties to achieve superior cancer diagnosis/phototheranostics applications are highlighted. Both the approaches of nanoengineering and molecular design, which can lead to optimized effectiveness of required biomedical function, are discussed.

Surface-adaptive nanoparticles with near-infrared aggregation-induced emission for image-guided tumor resection.

Aggregation-induced emission (AIE) nanoparticles (NPs) are widely used for image-guided tumor resection because of their high signal-to-noise ratios and long systemic circulation time. These NPs are derived by encapsulating small-molecule fluorescent dyes with AIE property inside the cores of NPs assembled by amphiphilic polymers. Although the systemic circulation of AIE NPs is prolonged, hydrophilic polymer coatings simultaneously decrease the binding and uptake of AIE NPs by tumor cells. To overcome this problem, surface-adaptive AIE dye-encapsulated mixed-shell micelles (MSMs) with polyethylene glycol/poly (ß-amino ester) (PEG/PAE) surfaces were prepared. Due to the charge conversion ability of PAE, MSMs demonstrated enhanced cellular uptake by tumor cells in acidic conditions. In addition, compared with single-PEG-shelled micelles (PEGSMs), MSMs exhibited prolonged systemic circulation due to the presence of micro-phase separated surfaces. Moreover, due to the co-ordination effect of enhanced cancer cell uptake and prolonged systemic circulation time, MSMs were more enriched than PEGSMs in the tumor cells and exhibited excellent performance during image-guided tumor resection.

Molecular Motion in Aggregates: Manipulating TICT for Boosting Photothermal Theranostics.

Planar donor and acceptor (D-A) conjugated structures are generally believed to be the standard for architecting highly efficient photothermal theranostic agents, in order to restrict intramolecular motions in aggregates (nanoparticles). However, other channels of extra nonradiative decay may be blocked. Now this challenge is addressed by proposing an "abnormal" strategy based on molecular motion in aggregates. Molecular rotors and bulky alkyl chains are grafted to the central D-A core to lower intermolecular interaction. The enhanced molecular motion favors the formation of a dark twisted intramolecular charge transfer state, whose nonradiative decay enhances the photothermal properties. Result shows that small-molecule NIRb14 with long alkyl chains branched at the second carbon exhibits enhanced photothermal properties compared with NIRb6, with short branched chains, and much higher than NIR6, with short linear chains, and the commercial gold nanorods. Both in vitro and in vivo experiments demonstrate that NIRb14 nanoparticles can be used as nanoagents for photoacoustic imaging-guided photothermal therapy. Moreover, charge reversal poly(ß-amino ester) makes NIRb14 specifically accumulate at tumor sites. This study thus provides an excited molecular motion approach toward efficient phototheranostic agents.

Axial modification inhibited H-aggregation of phthalocyanines in polymeric micelles for enhanced PDT efficacy.

Axial modified phthalocyanine (BtPc), aiming at avoiding H-aggregation and utilizing long wavelength light, was designed and synthesized. With the aid of polymer nanotechnology, BtPc loaded polymeric micelles with strong singlet oxygen generating ability and enhanced photodynamic therapy efficiency were developed. Optical characterizations and in vitro evaluations proved that the BtPc loaded polymeric micelles hold great potential for photodynamic therapy.