Chemiluminescence Resonance Energy Transfer Research Articles

Sensitive and on-Site Detection of Staphylococcus aureus Based on CRISPR/Cas 13a-Assisted Chemiluminescence Resonance Energy Transfer.

Developing a specific, sensitive, rapid, and on-site method for detecting pathogenic bacteria in food samples is critical to ensuring public safety. This article demonstrates a CRISPR/Cas13a system and a chemiluminescence resonance energy transfer (CRET) (CRISPR/Cas 13a-assisted CRET)-based strategy for sensitive and on-site detection of pathogenic bacteria in real samples. Once the hybrid double strand of aptamerS.aureus-cRNA recognizes the target model bacteria of Staphylococcus aureus (S. aureus), the released cRNA would bind with CRISPR/Cas 13a to form a complex of cRNA-CRISPR/Cas 13a, which could cleave the RNA molecule in the detecting probe of horseradish peroxidase (HRP) modified-gold nanoparticles (AuNPs) linked by RNA (AuNPs-RNA-HRP), resulting in an enhanced chemiluminescence signal due to the CRET "OFF" phenomenon after introducing the chemiluminescence substrate of luminol. The CRISPR/Cas 13a-assisted CRET strategy successfully detected S. aureus in drinking water and milk with detection limits of 20 and 30 cfu/mL, respectively, within the recovery of 90.07-105.50%. Furthermore, after integrating with an immunochromatographic test strip (ICTS), the CRISPR/Cas 13a-assisted CRET strategy achieved the on-site detection of as low as 102 cfu/mL of S. aureus in drinking water and milk via a smartphone, which is about 10 times lower than that in the previously reported AuNPs-based colorimetric ICTS, demonstrating a convenient and sensitive detection method for S. aureus in real samples.

Catalytic NIR chemiluminescence sensor with enhanced persistence and intensity for in vivo imaging

Chemiluminescence (CL) is a self-illumination phenomenon that involves the emission of light from chemical reactions, and it provides favorable spatial and temporal information on biological processes. However, it is still a great challenge to construct effective CL sensors that equip strong CL intensity, long emission wavelength, and persistent luminescence for deep tissue imaging. Here, we report a liposome encapsulated polymer dots (Pdots)-based system using catalytic CL substrates (L-012) as energy donor and fluorescent polymers and dyes (NIR 695) as energy acceptors for efficient Near-infrared (NIR) CL in vivo imaging. Thanks to the modulation of paired donor and acceptor distance and the slow diffusion of biomarker by liposome, the Pdots show a NIR emission wavelength (λ em, max = 720 nm), long CL duration (>24 h), and a high chemiluminescence resonance energy transfer efficiency (46.5 %). Furthermore, the liposome encapsulated Pdots possess excellent biocompatibility, sensitive response to H2O2, and persistent whole-body NIR CL imaging in the drug-induced inflammation and the peritoneal metastatic tumor mouse model. In a word, this NIR-II CL nanoplatform with long-lasting emission and high spatial-temporal resolution will be a concise strategy in deep tissue imaging and clinical diagnostics.

Tumor microenvironment activated and amplified self-luminescent nano photosensitizers for efficient treatment of triple negative breast cancer

Triple negative cancer (TNBC) is characterized as an aggressive phenotype lacking a specific therapeutic target. To date, self-illuminating photodynamic therapy (PDT) based on chemiluminescence resonance energy transfer (CRET) has emerged as a potential alternative for TNBC treatment by generating singlet oxygen (1O2), overcoming limitations in light penetration. However, this self-illuminating strategy heavily relies on endogenous hydrogen peroxide (H2O2) and oxygen (O2) within the tumor microenvironment (TME), resulting in inefficient therapeutic performance. In this study, we designed CLT@DPD nanoparticles capable of self-illumination via CRET and TME regulation through self-supplying H2O2 and O2. This nanoparticle was constructed by encapsulating luminol-tetreaphenylporphyrin conjugate (LT) and nanoscale CaO2 with DSPE-PEG 2000 and dioleoylphosphatidylcholine (DOPC). A good accumulation at tumor site was achieved due to enhanced permeability and retention (EPR) effect after intravenous injection of CLT@DP. Responsive to the high H2O2 levels and acidic aqueous conditions of TME, LT can be oxidized to produce 1O2via CRET, and the CaO2 can be decomposed to supply H2O2 and O2. Additionally, the presence of DOPC helps to enhance the permeability of the micelle shell under the oxidation of 1O2, thereby accelerating the release of H2O2 and O2. Our proposed nanoparticles exhibit excellent performance in eradicating in situ tumor cells and inhibiting metastasis by simultaneously enhancing self-luminous PDT and alleviating oxygen depletion in TME.

Near-Infrared Catalytic Chemiluminescence System based on Zinc Gallate Nanoprobe for Hydrazine Sensing.

To the deep tissue penetration and ultra-low background, developing near-infrared (NIR) chemiluminescence probes for human health and environmental safety has attracted more and more attention, but it remains a huge challenge. Herein, a novel NIR chemiluminescence (CL) system was rationally designed and developed, utilizing Cr3+-activated ZnGa2O4 (ZGC) nanoparticles as a catalytic luminophore via hypochlorite (NaClO) activation for poisonous target (hydrazine, N2H4) detection. With superior optical performance and unique catalytic structure of ZGC nanoparticles, the fabricated ZGC-NaClO-N2H4 CL system successfully demonstrated excellent NIR emission centered at 700 nm, fast response, and high sensibility (limit of detection down to 0.0126 μM). Further experimental studies and theoretical calculations found the cooperative catalytic chemiluminescence resonance energy transfer mechanism in the ZGC-NaClO-N2H4 system. Remarkably, the ZGC-based NIR CL system was further employed for N2H4 detection in a complicated matrix involving bioimaging and real water samples, thereby opening a new way as a highly reliable and accurate tool in biomedical and environmental monitoring applications.

Aggregation-Induced Emission-Based Chemiluminescence Systems in Biochemical Analysis and Disease Theranostics.

Chemiluminescence (CL) is of great significance in biochemical analysis and imaging due to its high sensitivity and lack of need for external excitation. In this review, we summarized the recent progress of AIE-based CL systems, including their working mechanisms and applications in biochemical analysis, bioimaging, and disease diagnosis and treatment. In ion and molecular detection, CL shows high selectivity and high sensitivity, especially in the detection of dynamic reactive oxygen species (ROS). Further, the integrated NIR-CL single-molecule system and nanostructural CL platform harnessing CL resonance energy transfer (CRET) have remarkable advantages in long-term imaging with superior capability in penetrating deep tissue depth and high signal-to-noise ratio, and are promising in the applications of in vivo imaging and image-guided disease therapy. Finally, we summarized the shortcomings of the existing AIE-CL system and provided our perspective on the possible ways to develop more powerful CL systems in the future. It can be highly expected that these promoted CL systems will play bigger roles in biochemical analysis and disease theranostics.

Chemiluminescent Conjugated Polymer Nanoparticles for Deep-Tissue Inflammation Imaging and Photodynamic Therapy of Cancer.

Deep-tissue optical imaging and photodynamic therapy (PDT) remain a big challenge for the diagnosis and treatment of cancer. Chemiluminescence (CL) has emerged as a promising tool for biological imaging and in vivo therapy. The development of covalent-binding chemiluminescence agents with high stability and high chemiluminescence resonance energy transfer (CRET) efficiency is urgent. Herein, we design and synthesize an unprecedented chemiluminescent conjugated polymer PFV-Luminol, which consists of conjugated polyfluorene vinylene (PFV) main chains and isoluminol-modified side chains. Notably, isoluminol groups with chemiluminescent ability are covalently linked to main chains by amide bonds, which dramatically narrow their distance, greatly improving the CRET efficiency. In the presence of pathologically high levels of various reactive oxygen species (ROS), especially singlet oxygen (1O2), PFV-Luminol emits strong fluorescence and produces more ROS. Furthermore, we construct the PFV-L@PEG-NPs and PFV-L@PEG-FA-NPs nanoparticles by self-assembly of PFV-Luminol and amphiphilic copolymer DSPE-PEG/DSPE-PEG-FA. The chemiluminescent PFV-L@PEG-NPs nanoparticles exhibit excellent capabilities for in vivo imaging in different inflammatory animal models with great tissue penetration and resolution. In addition, PFV-L@PEG-FA-NPs nanoparticles show both sensitive in vivo chemiluminescence imaging and efficient chemiluminescence-mediated PDT for antitumors. This study paves the way for the design of chemiluminescent probes and their applications in the diagnosis and therapy of diseases.

Traceable Lactate-Fueled Self-Acting Photodynamic Therapy against Triple-Negative Breast Cancer

The depth of light penetration and tumor hypoxia restrict the efficacy of photodynamic therapy (PDT) in triple-negative breast cancer (TNBC), while the overproduction of lactate (LA) facilitates the development, aggressiveness, and therapy resistance of TNBC. To address these issues, a self-acting PDT nanosystem (HL@hMnO 2 -LOx@HA) is fabricated by loading 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-alpha (HPPH), luminol, and LA oxidase (LOx) in a hyaluronic acid (HA)-coated hollow manganese dioxide (hMnO 2 ) nanoparticle. LOx catalyzes the oxidation of LA into pyruvate and hydrogen peroxide (H 2 O 2 ), thus depleting the overproduced intratumoral LA. In the acidic tumor microenvironment, H 2 O 2 reacts with luminol and hMnO 2 to yield blue luminescence as well as O 2 and Mn 2+ , respectively. Mn 2+ could further enhance this chemiluminescence. HPPH is then excited by the chemiluminescence through chemiluminescence resonance energy transfer for self-illuminated PDT. The generated O 2 alleviates the hypoxia state of the TNBC tumor to produce sufficient 1 O 2 for self-oxygenation PDT. The Mn 2+ performs T 1 magnetic resonance imaging to trace the self-acting PDT process. This work provides a biocompatible strategy to conquer the limits of light penetration and tumor hypoxia on PDT against TNBC as well as LA overproduction.

Shear Stress‐Triggered Theranostic Nanoparticles for Piezoelectric‐Fenton‐Photodynamic Thrombolysis and Endogenous Thrombus Imaging

AbstractThrombus therapy is challenged by potential bleeding risk of thrombolytic agents, and external irradiation is usually needed in thrombus imaging. Herein, highly efficient theranostic platforms are designed for piezoelectric‐Fenton‐photodynamic thrombolysis and endogenous thrombus imaging in response to the elevated shear stress at the thrombus site. Piezoelectric tetragonal barium titanate (tBT) nanoparticles (NPs) are coated with Fe3+‐coordinated metal‐organic frameworks (MOFs), followed by inoculation of chlorin e6‐luminol conjugates and heparin absorption to obtain theranostic tBT@MOFCL/Hep NPs. Shear stress‐induced piezopotential on NPs accelerates Fe3+/Fe2+ transformation to deplete MOF layers, activates Fenton reaction and produces reactive oxidative species (ROS) for non‐pharmacological thrombolysis. In the meantime, the site‐specific ROS generation oxidizes luminol and the chemiluminescent resonance energy transfer with chlorin e6 generates red fluorescence for thrombus imaging without using external light irradiation. After intravenous injection into a carotid artery thrombosis model, the heparin‐mediated thrombus targeting yields 6.5‐fold higher luminescent intensity at the thrombus site. Thrombi in the carotid arteries are almost completely dissolved with integration of piezoelectric dynamic therapy, piezopotential‐enhanced Fenton reaction, and chemiluminescence‐excited photodynamic therapy, while causing no haematologic and histopathologic abnormality. This study demonstrates a concise strategy to generate shear stress‐responsive built‐in piezoelectric potentials, site‐specific non‐pharmacological thrombolysis, self‐illuminating, and stenosis degree‐adaptable thrombus imaging.

CRISPR/Cas12a controlled chemiluminescence resonance energy transfer sensor for detection of carcinoembryonic antigen

A CRISPR-Cas12a controlled chemiluminescence resonance energy transfer (CRET) biosensor was constructed for the detection of cancer biomarker carcinoembryonic antigen (CEA). The CRET probe, a single-strand DNA (ssDNA) with hemin/G-quadruplex on one end and CdSe/ZnS quantum dots (QDs) nanosphere on the other end, was used as the substrate for the trans-cleavage of CRISPR/Cas12a system. The hemin/G-quadruplexes catalyzed the oxidation of luminol in the presence of H2O2. The generating chemiluminescence could excite the CdSe/ZnS QDs encapsulated in the nanosphere, producing CRET. When target CEA specifically identified dual aptamers on the surface of magnetic beads (MBs), the terminal sequence of Aptamer 2 triggered the hybridization chain reaction (HCR), whose product initiated the trans-cleavage activity of CRISPR/Cas12a and destroyed the CRET system. As a result, the luminescence of QDs nanosphere was declined. With HCR, CRISPR-Cas12a trans-cleavage, and mimic DNAzyme catalytic amplification, the biosensor gave a detection limit down to 5.6 pg/mL. Due to the application of CRISPR/Cas12a, the CRET sensor with the characteristics of easy operation and no external light source required was more suitable for point-of-care testing (POCT) detection of various targets.

A Porous Organic Framework‐Based Nanoplatform for Directional Destruction on Endoplasmic Reticulum to Enhance Tumor Immunotherapy

AbstractWith the development of oncology, immunotherapy holds great promise for tumor treatment. However, immunogenic cell death (ICD), an important stimulator of immune response, often fails to trigger effective immunotherapy. Herein, a strategy to cause endoplasmic reticulum (ER) stress for further amplifying ICD is reported. A porous organic framework‐based nanoplatform (PLGH‐TER) with good targeting ER ability for chemiluminescence resonance energy transfer (CRET) based‐photodynamic therapy (PDT) is developed, which solves the limitations of the restricted penetration of light and suboptimal bioavailability of commonly used photosensitizers (PS). Once accumulated in ER, PLGH‐TER activates the translation from glucose to H2O2 for starvation therapy and further elicit CRET‐based‐PDT, which results in ER stress and amplified ICD ultimately. Then, the amplified ICD promotes the release of damage‐associated molecular patterns , realizing enhanced immunotherapy. Consequently, PLGH‐TER can achieve directional destruction on ER and inhibit tumor invasion and recurrence, which expands the application of porous organic framework for tumor immunotherapy.

Escherichia coli-Based In Situ Triggerable Probe as an Amplifier for Sensitive Diagnosis and Penetrated Therapy of Cancer.

Escherichia coli (E. coli) was used for cancer therapy due to the tumor-targeting, catalytic, and surface-reducing properties. Effective diagnosis combined with treatment of cancer based on E. coli, however, was rarely demonstrated. In this study, E. coli was used to surface reduce HAuCl4 and as a carrier to modify riboflavin (Rf) and luminol (E-Au@Rf@Lum). After targeted delivery to tumor, the E-Au@Rf@Lum probe could actively emit 425 nm blue-violet chemiluminescence (CL) to achieve cell imaging for cancer diagnosis. Furthermore, this light could in situ trigger the photosensitizer (Rf) through CL resonance energy transfer, which produces reactive oxygen species (ROS) for accurate photodynamic therapy. In return, the excessive ROS enhanced the blue-violet light which was further absorbed by Rf, and ROS production was cyclically amplified. Abundant ROS broke down the dense extracellular matrix network and penetrated deep into tumors. Besides, E. coli with excellent catalytic property could decompose H2O2 to O2 to relieve tumor hypoxia for a long time and enhance the photosensitized process of Rf. By self-illumination, effective penetration, and tumor hypoxia relief, this work opens a self-amplified therapy modality to tumor.

Europium-Functionalized Graphitic Carbon Nitride for Efficient Chemiluminescence Detection of Singlet Oxygen.

Enhancing the sensitivity and selectivity of chemiluminescence (CL) sensors for detecting chemical species in complex samples poses a significant challenge in nanoparticle surface engineering. Graphitic carbon nitride (CN) shows promise but suffers from weak CL intensity and unknown luminescence mechanisms. In this study, we propose a nitrogen defect strategy to enhance the CL efficiency of europium-functionalized graphitic carbon nitride (Eu-CNNPs). By controlling the dosage of the europium modification, we can adjust the nitrogen defect content to reduce the energy gap and improve the CL performance. Remarkably, Eu-CNNPs with rich nitrogen defects exhibit strong chemiluminescence emission specifically for singlet oxygen (1O2) without responding to other reactive oxygen species (ROS). Building upon this finding, we developed a direct, selective, and sensitive CL sensing platform for 1O2 in PM2.5 and monitored 1O2 production in photosensitizers without interference from metal ions. Through extensive experiments, we attribute the 1O2-driven CL response to the presence of abundant nitrogen defects in the CN material, accelerating electron transfer and yielding a high generation of 1O2. Furthermore, chemiluminescence resonance energy transfer (CRET) between (1O2)2* (1O2 dimeric aggregate) and Eu-CNNPs contributes to strong CL emission. This work provides insights into enhancing the CL performance of CN and offers new possibilities for advancing the practical analysis of nanomaterials using the intriguing mechanism of nitrogen defects.

AIE Nanozyme-Based Long Persistent Chemiluminescence and Fluorescence for POCT of Pathogenic Bacteria.

Pathogenic bacteria are widely distributed in diverse environments and significantly threaten human health. Point-of-care testing (POCT) is a valuable way for early warnings of bacteria threat. Herein, a chemiluminescence (CL)-based ratiometric sensing platform was constructed for sensitive POCT of bacteria according to a newly designed aggregation-induced emission (AIE) molecule. The new AIE molecule presents oxidase-like properties (named as AIEzyme) and can trigger long persistent CL of luminol (LUM) with strong intensity in the absence of H2O2. The CL emission can be monitored with the naked eye for over 2 h. The emission mechanism is explored and may be attributed to the persistent reactive oxygen species generation of the AIEzyme according to the cyclic energy transfer between the AIEzyme and luminol, which catalyzes CL of luminol. Based on the CL resonance energy transfer mechanism, an afterglow luminescence system is further developed, which is used to construct a ratiometric biosensor for detection of pathogenic bacteria. With a homemade holder as a detection room and a smartphone as an analyzer, the portable biosensing platform is used for quantitative POCT of bacteria in real samples with good recovery. The detection is free of H2O2 and an external excitation source, which not only simplifies the operation but reduces interference. Specifically, the long persistent luminescence and the ratiometric strategy can significantly improve accuracy, providing an instructive way for point-of-need analysis, for example, SARS-CoV-2 detection and bioimaging analysis.

Host-Guest Interaction-Based Supramolecular Self-Assemblies for H2O2 Upregulation Augmented Chemiluminescence Resonance Energy Transfer-Induced Cancer Therapy.

Given that light is hard to reach deep tumor tissue, how to enhance photodynamic therapy (PDT) efficacy is a big challenge. Herein, we proposed the supramolecular polymer self-assemblies (HACP) with bis[2,4,5-trichloro-6 (pentyloxycar-bonyl) phenyl] oxalate as the cargos (HACP@CPPO) to realize the chemiluminescence resonance energy transfer (CRET)-induced generation of 1O2 in situ. HACP was prepared by cinnamaldehyde-modified hyaluronic acid (HA-CA) and β-cyclodextrin-modified protoporphyrin IX (β-CD-PPIX) via host-guest interactions. The CA moiety could elevate H2O2 levels for the enhanced production of chemical energy and macrocyclic CD could enhance the stacking distance of PPIX for enhanced 1O2 yield. Thus, HACP@CPPO exhibited excellent antitumor performance without light irradiation.

Pyrogallol Detection Based on the Cobalt Metal–Organic Framework of Nanomaterial-Enhanced Chemiluminescence

The cobalt metal–organic framework (Co-MOF) is a kind of crystalline porous material within a periodic network structure, which is formed via the self-assembly of a Co metal center and a bridged organic ligand. In this paper, a Co-MOF was facilely synthesized via an ultrasonic method and applied to enhance the chemiluminescence (CL) emission of the NaIO4-H2O2 system. The synthesized Co-MOF was nanosheet-like in nature and stacked in 2–3-micrometer flower shapes. Compared to the NaIO4-H2O2 system without a Co-MOF, the CL intensity of the Co-MOF-NaIO4-H2O2 system was enhanced about 70 times. This CL mechanism was determined to be a result of the synergistic effects of chemiluminescence resonance energy transfer (CRET) and electron–hole annihilation (EHA). The Co-MOF not only acted as a catalyst to accelerate the generation of reactive oxygen species in the CL reaction, but also worked as an emitter to further enhance the CL. Based on the Co-MOF-NaIO4-H2O2 system, a highly sensitive CL analysis method was established for pyrogallol (PG) detection. Addition of PG into the CL system generated 1O2*, which could transfer energy to the Co-MOF and further enhance the CL response. The enhanced CL was linear with the PG concentration. The CL analysis method exhibited a linear range of 1 × 10−4 M to 1 × 10−7 M, as well as having a linear correlation coefficient of 0.9995 and a limit of detection of (S/N = 3) of 34 nM.

Dextran-based micelles for combinational chemo-photodynamic therapy of tumors via in vivo chemiluminescence

Natural polysaccharides, represented by dextran, chitosan, and hyaluronic acid, are widely approved for use as pharmaceutical excipients and are important carrier materials for the design of advanced drug delivery systems, particularly in the field of anticancer drug delivery. The combination of stimuli-activable prodrug based chemotherapy and photodynamic therapy (PDT) has attracted increasing attention. Recent studies have verified the effectiveness of this strategy in the treatment of multiple aggressive cancers. However, in such combination, the stimuli-responsive chemotherapy and PDT have their own problems that need to be overcome. The uneven distribution of endogenous stimuli within tumor tissues makes it difficult for prodrug to be completely activated. And the inadequate tissue penetration depth of external light results in low efficiency of PDT. Aiming at these two bottlenecks, we designed a biocompatible dextran based - multi-component nanomedicine (PCL-NPs) that integrate a chemiluminescence agent luminol, a photosensitizer chlorine e6 (Ce6), and a reactive oxygen species (ROS)-activable thioketal-based paclitaxel (PTX) prodrug. The presence of overexpressed hydrogen peroxide (H2O2) inside tumor oxidizes the luminol moiety to generate in-situ light for PDT through chemiluminescence resonance energy transfer (CRET). The singlet oxygen (1O2) produced in this process not only directly kills tumor cells but also amplifies oxidative stress to accelerate the activation of PTX prodrug. We propose that the PCL-NPs have great therapeutic potential by simultaneously enhancing chemotherapy and PDT in a combination therapy.

Microfluidic paper chip based multicolor chemiluminescence sensing strategy for discrimination of antioxidants

The development of chemiluminescence (CL) sensing strategy with multiple-parameters for discrimination of small molecules remains a great challenge. Herein, a multicolor CL sensing strategy for the discrimination of five antioxidants, including dopamine, catechin, cysteine, glutathione, and thioctic acid was presented. Firstly, multilayer paper chips modified with luminol-Co(II), luminol-fluorescein-Co(II), and luminol-rhodamine B-Co(II) that can produce strong blue, green and purple colored light emission, respectively, via CL and CL resonance energy transfer (CRET) reactions were fabricated. The presence of antioxidants exhibits different inhibition or enhancement effect on the CL reactions, creating unique multicolor CL response pattern to each antioxidant. The red (R), green (G), and blue (B) channel split from the purple, green and blue CL image, respectively, generate cross-reactive sensing parameters for the discrimination of the five antioxidants. The distinct R, G, and B values of the CL images to each antioxidant are created as analytical fingerprints to identify five antioxidants by using principal component analysis and hierarchical cluster analysis. Satisfied results were obtained for discrimination antioxidant mixtures and spiked antioxidants in serum samples. Identification of 10 unknown samples resulted in 100% accuracy. This work presents the first example of multicolor CL sensing strategy for the discrimination of small molecules.

Self-Illuminating NIR-II Chemiluminescence Nanosensor for In Vivo Tracking H2 O2 Fluctuation.

Chemiluminescence (CL) imaging, as an excitation-free technique, exhibits a markedly improved signal-to-noise ratio (SNR) owing to the absence of an excitation light source and autofluorescence interference. However, conventional chemiluminescence imaging generally focuses on the visible and first near-infrared (NIR-I) regions, which hinders high-performance biological imaging due to strong tissue scattering and absorption. To address the issue, self-luminescent NIR-II CL nanoprobes with a second near-infrared (NIR-II) luminescence in the presence of hydrogen peroxide arerationally designed. A cascade energy transfer, including chemiluminescence resonance energy transfer (CRET) from the chemiluminescent substrate to NIR-I organic molecules and Förster resonance energy transfer (FRET) from NIR-I organic molecules to NIR-II organic molecules, occurs in the nanoprobes, contributing to NIR-II light with great efficiency and good tissue penetration depth. Based on excellent selectivity, high sensitivity to hydrogen peroxide, and long-lasting luminescence performance, the NIR-II CL nanoprobes areapplied to detect inflammation in mice, showing a 7.4-fold enhancement in SNR compared with that of fluorescence.

Supramolecularly Engineered Reporters with Superoxide Anion‐Triggered Chemiluminescence for Early Diagnosis and Efficient Amelioration of Acute Kidney Injury

AbstractWe report the “water‐in‐oil‐in‐water” preparation of kidney injury molecule‐1‐targeting supramolecular chemiluminescence (CL) reporters (PCCS), consisting of L‐serine‐modified poly(lactic‐co‐glycolic) acid (PLGA)‐encapsulated peroxyoxalate (CPPO), chlorin e6 (Ce6) and superoxide dismutase (SOD), for early diagnosis and amelioration of acute kidney injury (AKI). In this system, O2⋅−, a biomarker of AKI, triggers the oxidation of CPPO to 1,2‐dioxetanedione and subsequent CL emission via CL resonance energy transfer to Ce6. The L‐serine‐modified PLGA stabilizes CPPO and Ce6 via noncovalent interactions, promoting long‐lived CL (half‐lives: ≈1000 s). Transcriptomics analysis shows that PCCS reporters reduce the inflammatory response through glutathione metabolism and inhibition of the tumor necrosis factor signaling pathway. The reporters are able to non‐invasively detect AKI at least 12 h earlier than current assays, and their antioxidant properties allow simultaneous treatment of AKI.

Supramolecularly Engineered Reporters with Superoxide Anion-Triggered Chemiluminescence for Early Diagnosis and Efficient Amelioration of Acute Kidney Injury.

We report the "water-in-oil-in-water" preparation of kidney injury molecule-1-targeting supramolecular chemiluminescence (CL) reporters (PCCS), consisting of L-serine-modified poly(lactic-co-glycolic) acid (PLGA)-encapsulated peroxyoxalate (CPPO), chlorin e6 (Ce6) and superoxide dismutase (SOD), for early diagnosis and amelioration of acute kidney injury (AKI). In this system, O2 ⋅- , a biomarker of AKI, triggers the oxidation of CPPO to 1,2-dioxetanedione and subsequent CL emission via CL resonance energy transfer to Ce6. The L-serine-modified PLGA stabilizes CPPO and Ce6 via noncovalent interactions, promoting long-lived CL (half-lives: ≈1000 s). Transcriptomics analysis shows that PCCS reporters reduce the inflammatory response through glutathione metabolism and inhibition of the tumor necrosis factor signaling pathway. The reporters are able to non-invasively detect AKI at least 12 h earlier than current assays, and their antioxidant properties allow simultaneous treatment of AKI.