ABSTRACT
Catalytic therapy has shown great potential for clinical application. However, conventional catalytic therapies rely on reactive oxygen species (ROS) as "therapeutic drugs," which have limitations in effectively inhibiting tumor recurrence and metastasis. Here, a biomimetic heterojunction catalyst is developed that can actively target orthotopic rectal cancer after oral administration. The heterojunction catalyst is composed of quatrefoil star-shaped BiVO4 (BVO) and ZnIn2S4 (ZIS) nanosheets through an in situ direct growth technique. Poly-norepinephrine and macrophage membrane coatings afford the biomimetic heterojunction catalyst (BVO/ZIS@M), which has high rectal cancer targeting and retention abilities. The coupled optical fiber intervention technology activates the multicenter coordination of five catalytic reactions of heterojunction catalysts, including two reduction reactions (O2â·O2 - and CO2âCO) and three oxidation reactions (H2Oâ·OH, GSHâGSSG, and LAâPA). These catalytic reactions not only induce immunogenic death in tumor cells through the efficient generation of ROS/CO and the consumption of GSH but also specifically lead to the use of lactic acid (LA) as an electron donor to improve catalytic activity and disrupt the LA-mediated immunosuppressive microenvironment, mediating synergistic catalysis and immunotherapy for orthotopic rectal cancer. Therefore, this optical fiber intervention triggered the combination of heterojunction catalytic therapy and immunotherapy, which exhibits prominent antitumor effects.
ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Qiling granules (FQG), derived from the traditional Qiling Decoction with a longstanding clinical history, is utilized for the treatment of hyperuricemia (HUA). FQG is formulated with a combination of seven Chinese herbs based on the principles of traditional Chinese medicine (TCM) theories. Clinical evidence indicates that FQG exhibits favorable therapeutic effects in reducing uric acid (UA) levels and attenuating renal damage. AIM OF THIS STUDY: To elucidate the potential active components and pharmacological mechanism of FQG in the treatment of HUA, and to provide an experimental basis for the development of efficient and low-toxicity TCM for HUA treatment. MATERIALS AND METHODS: A HUA rat model induced by potassium oxonate and adenine was established to initially evaluate the hypouricemic effects of FQG. Chemical analyses were conducted using an ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Network pharmacology was used to investigate the active components and mechanism of FQG in the treatment of HUA. Potential Xanthine oxidase (XOD) inhibitors were screened from FQG based on ultrafiltration liquid chromatography and mass spectrometry (UF-LC-MS). Molecular docking, surface plasmon resonance (SPR) and circular dichroism (CD) spectroscopy were applied to validate the interactions between the active components and XOD. RESULTS: In comparison to the model group, treatment with FQG significantly decreased serum UA, serum creatinine (CREA), serum blood urea nitrogen (BUN), and liver XOD activity. Additionally, the FQG administration notably ameliorated HUA-induced renal injury in rats. Through the pharmacodynamics of the HUA rat models and network pharmacology, it was found that XOD was a key pathway enzyme in UA metabolism. 18 XOD inhibitors were screened from FQG by UF-LC-MS, and 11 compounds with strong affinity were verified by SPR, molecular docking and CD spectroscopy. CONCLUSION: In summary, flavonoids, organic acids and saponins may be the active components in FQG that alleviate HUA. The primary mechanism of FQG involves inhibiting XOD enzyme activity in the plasma to reduce UA production, alleviating renal tubular epithelial cell necrosis, tubulointerstitial injury, fibrosis, and urate deposition, ultimately exerting a therapeutic effect on HUA.
Subject(s)
Drugs, Chinese Herbal , Hyperuricemia , Xanthine Oxidase , Animals , Male , Rats , Disease Models, Animal , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Enzyme Inhibitors/pharmacology , Hyperuricemia/drug therapy , Hyperuricemia/chemically induced , Molecular Docking Simulation , Network Pharmacology , Oxonic Acid , Rats, Sprague-Dawley , Uric Acid/blood , Xanthine Oxidase/metabolism , Xanthine Oxidase/antagonists & inhibitorsABSTRACT
Spirolactones are widely found in pharmaceuticals and bioactive natural products. However, efficient and environmentally friendly approaches to accessing spirolactones are still highly desirable. Herein, a novel electrochemical synthesis of spirolactones from α-tetralone derivatives with methanol as a C1 source is described. This electrochemical reaction exhibits a high efficiency and good functional group tolerance.
ABSTRACT
Lactic acid (LA) accumulation in the tumor microenvironment poses notable challenges to effective tumor immunotherapy. Here, an intelligent tumor treatment microrobot based on the unique physiological structure and metabolic characteristics of Veillonella atypica (VA) is proposed by loading Staphylococcus aureus cell membrane-coating BaTiO3 nanocubes (SAM@BTO) on the surface of VA cells (VA-SAM@BTO) via click chemical reaction. Following oral administration, VA-SAM@BTO accurately targeted orthotopic colorectal cancer through inflammatory targeting of SAM and hypoxic targeting of VA. Under in vitro ultrasonic stimulation, BTO catalyzed two reduction reactions (O2 â â¢O2- and CO2 â CO) and three oxidation reactions (H2O â â¢OH, GSH â GSSG, and LA â PA) simultaneously, effectively inducing immunogenic death of tumor cells. BTO catalyzed the oxidative coupling of VA cells metabolized LA, effectively disrupting the immunosuppressive microenvironment, improving dendritic cell maturation and macrophage M1 polarization, and increasing effector T cell proportions while decreasing regulatory T cell numbers, which facilitates synergetic catalysis and immunotherapy.
Subject(s)
Barium Compounds , Biomimetic Materials , Colorectal Neoplasms , Immunosuppression Therapy , Nanotubes , Robotics , Titanium , Tumor Microenvironment , Veillonella , Biomimetic Materials/administration & dosage , Catalysis , Colorectal Neoplasms/drug therapy , Staphylococcus aureus , Nanotubes/chemistry , Titanium/administration & dosage , Titanium/pharmacology , Barium Compounds/administration & dosage , Barium Compounds/pharmacology , Cell Membrane/chemistry , Administration, Oral , Oxidation-Reduction , Immunosuppression Therapy/methods , Tumor Microenvironment/drug effects , Tumor Microenvironment/immunology , Lactic Acid/metabolism , Humans , Cell Line, TumorABSTRACT
Development of non-surgical treatment of human abdominal aortic aneurysm (AAA) has clinical significance. Colchicine emerges as an effective therapeutic regimen in cardiovascular diseases. Yet, whether colchicine slows AAA growth remain controversy. Here, we demonstrated that daily intragastric administration of low-dose colchicine blocked AAA formation, prevented vascular smooth muscle cell (SMC) phenotype switching and apoptosis, and vascular inflammation in both peri-aortic CaPO4 injury and subcutaneous angiotensin-II infusion induced experimental AAA mice models. Mechanistically, colchicine increased global mRNA stability by inhibiting the METTL14/YTHDC1-mediated m6A modification, resulting in increased sclerostin (SOST) expression and consequent inactivation of the WNT/ß-catenin signaling pathway in vascular SMCs from mouse AAA lesions and in cultured human aortic SMCs. Moreover, human and mouse AAA lesions all showed increased m6A methylation, decreased SOST expression, and skewed synthetic SMC de-differentiation phenotype, compared to those without AAA. This study uncovers a novel mechanism of colchicine in slowing AAA development by using the METTL14/SOST/WNT/ß-catenin axis to control vascular SMC homeostasis in mouse aortic vessels and in human aortic SMCs. Therefore, use of colchicine may benefit AAA patients in clinical practice.
Subject(s)
Aortic Aneurysm, Abdominal , Muscle, Smooth, Vascular , Humans , Animals , Mice , Aortic Aneurysm, Abdominal/drug therapy , Homeostasis , Aorta , Colchicine/therapeutic useABSTRACT
The precise targeted delivery of therapeutic agents to deep regions of the brain is crucial for the effective treatment of various neurological diseases. However, achieving this goal is challenging due to the presence of the bloodâbrain barrier (BBB) and the complex anatomy of the brain. Here, a biomimetic self-propelled nanomotor with cascade targeting capacity is developed for the treatment of neurological inflammatory diseases. The self-propelled nanomotors are designed with biomimetic asymmetric structures with a mesoporous SiO2 head and multiple MnO2 tentacles. Macrophage membrane biomimetic modification endows nanomotors with inflammatory targeting and BBB penetration abilities The MnO2 agents catalyze the degradation of H2O2 into O2, not only by reducing brain inflammation but also by providing the driving force for deep brain penetration. Additionally, the mesoporous SiO2 head is loaded with curcumin, which actively regulates macrophage polarization from the M1 to the M2 phenotype. All in vitro cell, organoid model, and in vivo animal experiments confirmed the effectiveness of the biomimetic self-propelled nanomotors in precise targeting, deep brain penetration, anti-inflammatory, and nervous system function maintenance. Therefore, this study introduces a platform of biomimetic self-propelled nanomotors with inflammation targeting ability and active deep penetration for the treatment of neurological inflammation diseases.
Subject(s)
Biomimetics , Blood-Brain Barrier , Silicon Dioxide , Animals , Silicon Dioxide/chemistry , Mice , Biomimetics/methods , Blood-Brain Barrier/metabolism , Manganese Compounds/chemistry , Biomimetic Materials/chemistry , Drug Delivery Systems/methods , Oxides/chemistry , Curcumin/therapeutic use , Curcumin/pharmacology , Disease Models, Animal , Neuroinflammatory Diseases , Inflammation , Macrophages , Brain/metabolism , Nanoparticles/chemistryABSTRACT
Chronic diabetic wounds are at lifelong risk of developing diabetic foot ulcers owing to severe hypoxia, excessive reactive oxygen species (ROS), a complex inflammatory microenvironment, and the potential for bacterial infection. Here we develop a programmed treatment strategy employing live Haematococcus (HEA). By modulating light intensity, HEA can be programmed to perform a variety of functions, such as antibacterial activity, oxygen supply, ROS scavenging, and immune regulation, suggesting its potential for use in programmed therapy. Under high light intensity (658 nm, 0.5 W/cm2), green HEA (GHEA) with efficient photothermal conversion mediate wound surface disinfection. By decreasing the light intensity (658 nm, 0.1 W/cm2), the photosynthetic system of GHEA can continuously produce oxygen, effectively resolving the problems of hypoxia and promoting vascular regeneration. Continuous light irradiation induces astaxanthin (AST) accumulation in HEA cells, resulting in a gradual transformation from a green to red hue (RHEA). RHEA effectively scavenges excess ROS, enhances the expression of intracellular antioxidant enzymes, and directs polarization to M2 macrophages by secreting AST vesicles via exosomes. The living HEA hydrogel can sterilize and enhance cell proliferation and migration and promote neoangiogenesis, which could improve infected diabetic wound healing in female mice.
Subject(s)
Diabetes Mellitus , Diabetic Foot , Microalgae , Female , Animals , Mice , Reactive Oxygen Species , Anti-Bacterial Agents/pharmacology , Hypoxia , Oxygen , Wound Healing , HydrogelsABSTRACT
[This corrects the article DOI: 10.1371/journal.pone.0293500.].
ABSTRACT
BACKGROUND: Recent studies reveal that dietary fiber (DF) might play a critical role in the metabolism and bioactivity of flavonoids by regulating gut microbiota. We previously found that Shatianyu (Citrus grandis L. Osbeck) pulp was rich in flavonoids and DF, and Shatianyu pulp flavonoid extracts (SPFEs) were dominated by melitidin, obviously different from other citrus flavonoids dominated by naringin. The effects of Shatianyu pulp DF (SPDF) on the microbial metabolism and bioactivity of SPFEs is unknown. RESULTS: An in vitro colonic fermentation model was used to explore the effects of SPDF on the microbial metabolism and antioxidant activity of SPFEs in the present study. At the beginning of fermentation, SPDF promoted the microbial degradation of SPFEs. After 24 h-fermentation, the supplemented SPFEs were almost all degraded in SPFEs group, and the main metabolites detected were the dehydrogenation, hydroxylation and acetylation products of naringenin, the aglycone of the major SPFEs components. However, when SPFEs fermented with SPDF for 24 h, 60.7% of flavonoid compounds were retained, and SPFEs were mainly transformed to the ring fission metabolites, such as 3-(4-hydroxyphenyl) propionic acid, 3-phenylpropionic acid and 3-(3-hydroxy-phenyl) propionic acid. The fermentation metabolites of SPFEs showed stronger antioxidant activity than the original ones, with a further increase in SPDF supplemented group. Furthermore, SPFEs enriched microbiota participating in the deglycosylation and dehydrogenation of flavonoids, while co-supplementation of SPDF and SPFEs witnessed the bloom of Lactobacillaceae and Lactobacillus, contributing to the deglycosylation and ring fission of flavonoids. CONCLUSION: SDPF promote SPFEs to transform to active metabolites probably by regulating gut microbiota. © 2023 Society of Chemical Industry.
Subject(s)
Citrus , Flavonoids , Phenols , Propionates , Flavonoids/chemistry , Citrus/chemistry , Antioxidants/metabolism , Fermentation , Dietary FiberABSTRACT
The landscape of financial technology is undergoing a continuous evolution, driven by the relentless advancement of information technology. In this transformative milieu, digital finance has emerged as a novel financial paradigm, offering a blueprint for fostering inclusive finance. With a particular emphasis on its implications for Small and Medium-sized Enterprises (SMEs), this article harnesses a comprehensive dataset spanning the years 2011 to 2021, encompassing digital inclusive finance and SMEs listed on the SME board. Employing fixed effects models, this study performs a regression analysis to verify the driving effect of digital inclusive finance on SMEs' innovation activities. The findings unequivocally affirm the potency of inclusive finance in ameliorating the longstanding financing constraints that have historically constrained the growth trajectory of SMEs. Furthermore, the study elucidated the nuanced nature of the promotional impact of digital inclusive finance on SMEs, contingent upon their distinct property rights and technological attributes. Specifically, the empirical findings unveil a discernible pattern wherein digital inclusive finance exerts a conspicuously stronger promotional effect on non-state-owned enterprises and high-tech SMEs' endeavors in technological innovation. The conclusions derived from this research furnish a salient point of reference for governmental authorities engaged in the formulation and advancement of digital inclusive finance strategies, thereby imparting strategic guidance for the cultivation of innovation and holistic development within the SME sector.
Subject(s)
Inventions , Rehabilitation, Vocational , Humans , Technology , Government , Group Processes , ChinaABSTRACT
In this study, ß-CD was used as a receptor to prepare three novel SDES, which were used to pretreat corn stalks for obtaining fluorescent lignin and promoting biomass pyrolytic saccharification. It was found that GA-residue had a high cellulose retention ratio (94.63%) and the highest lignin removal ratio (61.78%). Besides, the yield of carbohydrates in bio-oil was increased from 0.63% to 49.37%, and fluorescent lignin was prepared for explosion detection, fluorescent film, and information encryption. It was confirmed that the weak interaction between ß-CD and HBDs or dimer was mainly performed by hydrogen bond and van der Waals force. The minimum frontier orbital energy difference ΔEU (0.1976 a.u.) and high binding energy (-5456.71 kJ/mol) between molecules were calculated by DFT. Moreover, the mechanism of biomass pretreatment was explored. The green and efficient SDES developed in this study were of great significance for biomass pretreatment and efficient utilization of components.
ABSTRACT
The exogenous excitation requirement and electron-hole recombination are the key elements limiting the application of catalytic therapies. Here a tumor microenvironment (TME)-specific self-triggered thermoelectric nanoheterojunction (Bi0.5Sb1.5Te3/CaO2 nanosheets, BST/CaO2 NSs) with self-built-in electric field facilitated charge separation is fabricated. Upon exposure to TME, the CaO2 coating undergoes rapid hydrolysis, releasing Ca2+, H2O2, and heat. The resulting temperature difference on the BST NSs initiates a thermoelectric effect, driving reactive oxygen species production. H2O2 not only serves as a substrate supplement for ROS generation but also dysregulates Ca2+ channels, preventing Ca2+ efflux. This further exacerbates calcium overload-mediated therapy. Additionally, Ca2+ promotes DC maturation and tumor antigen presentation, facilitating immunotherapy. It is worth noting that the CaO2 NP coating hydrolyzes very slowly in normal cells, releasing Ca2+ and O2 without causing any adverse effects. Tumor-specific self-triggered thermoelectric nanoheterojunction combined catalytic therapy, ion interference therapy, and immunotherapy exhibit excellent antitumor performance in female mice.
Subject(s)
Hydrogen Peroxide , Neoplasms , Female , Animals , Mice , Immunotherapy , Neoplasms/therapy , Antigen Presentation , Biological Transport , Tumor MicroenvironmentABSTRACT
Natural products has been used for the prevention and treatment of diseases for a long history. Research on the bioactive components from natural products and their interaction with target proteins are essential for drug discovery. However, studying the binding ability of natural products' active ingredients to target proteins is usually time-consuming and laborious due to their complex and diverse chemical structures. In this study, we have developed a high resolution micro-confocal Raman spectrometer-based photo-affinity microarray (HRMR-PM) technology for the investigation of active ingredients-target protein recognition strategy. The novel photo-affinity microarray was constructed by photo-cross-linking the small molecule with the photo-affinity group (4-[3-(Trifluoromethyl)-3H-diazirin-3-yl]benzoic acid, TAD) on the photo-affinity linker coated (PALC) slides under 365 nm ultraviolet irradiation. The small molecules on the microarrays with specific binding ability might immobilize target protein, which were characterized by high resolution micro-confocal Raman spectrometer. Using this method, more than a dozen components of Shenqi Jiangtang granules (SJG) were made into small molecule probe (SMP) microarrays. As a result, 8 of them had been identified to have α-glucosidase binding ability according to characteristic Raman shift at about 3060 cm-1. These compounds were further verified by different small molecule-protein interaction analysis methods, including contact angle D-value, surface plasmon resonance (SPR) and molecular docking. The results showed that Ginsenosides Mb, Formononetin and Gomisin D exhibited the strongest binding ability. In conclusion, the HRMR-PM strategy for investigating the interaction between target proteins and small molecules has the advantages such as high throughput, low sample consumption and fast qualitative characterization. This strategy is universal which can be applied in the study of in vitro binding activity of various types of small molecules to target proteins.
Subject(s)
Proteins , alpha-Glucosidases , Molecular Docking Simulation , Proteins/chemistryABSTRACT
Radiosensitizers potentiate the radiotherapy effect while effectively reducing the damage to healthy tissues. However, limited sample accumulation efficiency and low radiation energy deposition in the tumor significantly reduce the therapeutic effect. Herein, we developed multifunctional photocatalysis-powered dandelion-like nanomotors composed of amorphous TiO2 components and Au nanorods (â¼93 nm in length and â¼16 nm in outer diameter) by a ligand-mediated interface regulation strategy for NIR-II photoacoustic imaging-guided synergistically enhanced cancer radiotherapy. The non-centrosymmetric nanostructure generates stronger local plasmonic near-fields close to the Au-TiO2 interface. Moreover, the Au-TiO2 Schottky heterojunction greatly facilitates the separation of photogenerated electron-hole pairs, enabling hot electron injection, finally leading to highly efficient plasmon-enhanced photocatalytic activity. The nanomotors exhibit superior motility both in vitro and in vivo, propelled by H2 generated via NIR-catalysis on one side of the Au nanorod, which prevents them from returning to circulation and effectively improves the sample accumulation in the tumor. Additionally, a high radiation dose deposition in the form of more hydroxyl radical generation and glutathione depletion is authenticated. Thus, synergistically enhanced radiotherapeutic efficacy is achieved in both a subcutaneous tumor model and an orthotopic model.
ABSTRACT
Inorganic nanoprobes have attracted increasing attention in the biomedical field due to their versatile functionalities and excellent optical properties. However, conventional nanoprobes have a relatively low retention time in the tumor and are mostly applied in the first near-infrared window (NIR-I, 650-950 nm), limiting their applications in accurate and deep tissue imaging. Herein, we develop a Janus nanoprobe, which can undergo tumor microenvironment (TME)-induced aggregation, hence, promoting tumor retention time and providing photoacoustic (PA) imaging in the second NIR (NIR-II, 950-1700 nm) window, and enhancing photodynamic therapy (PDT) effect. Ternary Janus nanoprobe is composed of gold nanorod (AuNR) coated with manganese dioxide (MnO2) and photosensitizer pyropheophorbide-a (Ppa) on two ends of AuNR, respectively, named as MnO2-AuNR-Ppa. In the tumor, MnO2 could be etched by glutathione (GSH) to release Mn2+, which is coordinated with multiple Ppa molecules to induce in situ aggregation of AuNRs. The aggregation of AuNR effectively improves the NIR-II photoacoustic signal in vivo. Moreover, the increased retention time of nanoprobes and GSH reduction in the tumor greatly improve the PDT effect. We believe that this work will inspire further research on specific in situ aggregation of inorganic nanoparticles.
Subject(s)
Nanoparticles , Neoplasms , Photoacoustic Techniques , Photochemotherapy , Glutathione , Humans , Manganese Compounds , Neoplasms/diagnostic imaging , Neoplasms/drug therapy , Oxides , Photoacoustic Techniques/methods , Tumor MicroenvironmentABSTRACT
Heteroatom interaction of atomically thin nanomaterials enables the improvement of electronic transfer, band structure, and optical properties. Black phosphorus quantum dots (BP QDs) are considered to be candidate diagnostic and/or therapeutic agents due to their innate biocompatibility and exceptional photochemical effects. However, BP QDs are not competitive regarding second near-infrared (NIR-II) window medical diagnosis and X-ray induced phototherapy. Here, an Nd3+ ion coordinated BP QD (BPNd) is synthesized with the aim to sufficiently improve its performances in NIR-II fluorescence imaging and X-ray induced photodynamic therapy, benefitting from the retrievable NIR/X-ray optoelectronic switching effects between BP QD and Nd3+ ion. Given its ultrasmall size and efficient cargo loading capacity, BPNd can easily cross the blood-brain barrier to precisely monitor the growth of glioblastoma through intracranial NIR-II fluorescence imaging and impede its progression by specific X-ray induced, synergistic photodynamic chemotherapy.
Subject(s)
Glioblastoma , Quantum Dots , Glioblastoma/diagnostic imaging , Humans , Neodymium , Phosphorus/chemistry , Quantum Dots/chemistry , X-RaysABSTRACT
Photoacoustic imaging (PA) in the second near infrared (NIR-II) window presents key advantages for deep tissue imaging owing to reduced light scattering and low background signal from biological structures. Here, a thiadiazoloquinoxaline-based semiconducting polymer (SP) with strong absorption in the NIR-II region is reported. After encapsulation of SP in Pluronic F127 (F127) followed by removal of excess surfactant, a dual functional polymer system named surfactant-stripped semiconductor polymeric micelles (SSS-micelles) are generated with water solubility, storage stability, and high photothermal conversion efficiency, permitting tumor theranostics in a mouse model. SSS-micelles have a wideband absorption in the NIR-II window, allowing for the PA imaging at both 1064 and 1300 nm wavelengths. The PA signal of the SSS-micelles can be detected through 6.5 cm of chicken breast tissue in vitro. In mice or rats, SSS-micelles can be visualized in bladder and intestine overlaid 5 cm (signal to noise ratio, SNR ≈ 17 dB) and 5.8 cm (SNR over 10 dB) chicken breast tissue, respectively. This work demonstrates the SSS-micelles as a nanoplatform for deep tissue theranostics.
Subject(s)
Nanoparticles , Neoplasms , Photoacoustic Techniques , Animals , Mice , Micelles , Nanoparticles/chemistry , Neoplasms/diagnostic imaging , Neoplasms/therapy , Photoacoustic Techniques/methods , Phototherapy , Polymers/chemistry , Precision Medicine , Rats , Surface-Active Agents/chemistryABSTRACT
Biocompatible nano-antioxidants composed of natural molecules/materials, such as dopamine and melanin, are of great interest for diverse biomedical applications. However, the lack of understanding of the precise structure of these biomaterials and thus the actual dose of effective components impedes their advancement to translation. Herein, a strategy to mimic in situ melanin formation and explore its antioxidative applications is reported, by developing a PEGylated, phenylboronic-acid-protected L-DOPA precursor (PAD) that can self-assemble into well-defined nanoparticles (PADN). Exposure to oxidative species leads to deprotection of phenylboronic acids, transforming PADN to PEG-L-DOPA, which, similar to the biosynthetic pathway of melanin, can be oxidized and polymerized into an antioxidative melanin-like structure. With ultrahigh stability and superior antioxidative activity, the PADN shows remarkable efficacy in prevention and treatment of acute liver injury/failure. Moreover, the in situ structure transformation enables PADN to visualize damaged tissue noninvasively by photoacoustic imaging. Overall, a bioinspired antioxidant with precise structure and site-specific biological activity for theranostics of oxidative stress-related diseases is described.
Subject(s)
Antioxidants/chemistry , Liver Failure, Acute/diagnostic imaging , Liver Failure, Acute/therapy , Melanins/chemistry , Animals , Apoptosis , Hydrogen Peroxide/chemistry , Levodopa/chemistry , Liver , Liver Failure, Acute/metabolism , Magnetic Resonance Spectroscopy , Male , Membrane Potentials , Mice , Mice, Inbred BALB C , Microscopy, Electron, Transmission , Nanoparticles/chemistry , Oxidative Stress , Oxygen/chemistry , Photoacoustic Techniques/methods , Polyethylene Glycols/chemistry , RAW 264.7 Cells , Reactive Oxygen Species , Theranostic Nanomedicine , Treatment OutcomeABSTRACT
Wilson's disease (WD) is a rare inherited disorder of copper metabolism with pathological copper hyperaccumulation in some vital organs. However, the clinical diagnosis technique of WD is complicated, aggressive, and time-consuming. In this work, a novel ratiometric photoacoustic (PA) imaging nanoprobe in the NIR-II window is developed to achieve noninvasive, rapid, and accurate Cu2+ quantitative detection in vitro and in vivo. The nanoprobe consists of Cu2+ -responsive IR970 dye and a nonresponsive palladium-coated gold nanorod (AuNR-Pd), achieving a concentration-dependent ratiometric PA970 /PA1260 signal change. The urinary Cu2+ content is detectable within minutes down to a detection limit of 76 × 10-9 m. This report acquisition time is several orders of magnitude shorter than those of existing detection approaches requiring complex procedure. Moreover, utilizing the ratiometric PA nanoprobe, PA imaging enables biopsy-free measurement of the liver Cu2+ content and visualization of the liver Cu2+ biodistribution of WD patient, which avoid the body injury during the clinical Cu2+ test using liver biopsy method. The NIR-II ratiometric PA detection method is simple and noninvasive with super precision, celerity, and simplification, which holds great promise as an alternative to liver biopsy for clinical diagnosis of WD.
Subject(s)
Hepatolenticular Degeneration , Biopsy , Copper , Gold , Hepatolenticular Degeneration/diagnostic imaging , Humans , Tissue DistributionABSTRACT
To date, hydrogen (H2 ) therapy has received widespread attention. However, X-ray triggered sustainable H2 -producing materials with controlled release for cancer treatment have not been reported. Herein, an X-ray triggered sustainable in situ H2 producing platform, Au NR-TiO2 @ZnS:Cu,Co-A(Au-TiO2 @ZnS), composed of Au-amorphous TiO2 nano-dumbbell-shaped heterostructure coated with long afterglow particles, was developed for cancer synergistic H2 -radiotherapy. The mechanism of H2 production was verified by theoretical calculations and in vitro experiments. Changes in the apoptosis pathway caused by the synergistic effect of H2 and radiotherapy were reported. Guided by its excellent photoacoustic imaging capabilities, mice with orthotopic liver cancer achieved excellent therapeutic effects and low inflammatory side effects, suggesting that Au-TiO2 @ZnS has promising application potential for cancer treatment and prognosis.