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MSOT/CT/MR imaging Guided and hypoxia Maneuvered Oxygen self-sufficiency radiotherapy based on One-pot MnO2-mSiO2 @ Au nanoparticle
摘要： Radiotherapy (RT) is one of the most widely applied treatments for cancer therapy in the clinic. Herein, we constructed an innovative multifunctional nanotheranostic MnO2-mSiO2@Au-HA nanoparticles (MAHNPs) based on one-pot MnO2-mSiO2 nanohybrids (MNHs) and gold nanoparticles (AuNPs) for multispectral optoacoustic tomography (MSOT)/ computed tomography (CT) and magnetic resonance (MR) imaging guided hypoxia-maneuvered radiotherapy. The MNHs were prepared by a facile one-pot approach which avoided the leakage of MnO2 nanoparticles as well as increased the efficiency on preparation. The Mn2+ ions could trigger the breakdown of endogenous H2O2 to generate O2 to convert the hypoxic tumor micro-environment (TME), thus enhancing radiotherapy by self-sufficiency oxygen. In addition, hyaluronic acid (HA) was employed to modify the surface of MnO2-mSiO2@Au nanoparticles to improve biocompatibility and cellular uptake. The well-designed nanoparticles could perform remarkable photothermal therapy (PTT) and hypoxia-maneuvered radiotherapy (RT) simultaneously as well as MSOT/CT/MR imaging. In vivo studies showed that MAHNPs achieved almost entirely suppression of tumor growth without observable recurrence, which raised new possibilities for clinical nanotheranostics with multimodal diagnostic and therapeutic coalescent design.
关键词： photothermal therapy (PTT),gold nanoparticles,nanotheranostics,MSOT/CT/MR imaging,hypoxia-maneuvered radiotherapy,MnO2-mSiO2 nanohybrids
更新于2025-11-19 16:56:35
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Perfluorocarbon-Loaded and Redox-Activatable Photosensitizing Agent with Oxygen Supply for Enhancement of Fluorescence/Photoacoustic Imaging Guided Tumor Photodynamic Therapy
摘要： The wide clinical application of photodynamic therapy (PDT) is hampered by poor water solubility, low tumor selectivity, and nonspecific activation of photosensitizers, as well as tumor hypoxia which is common for most solid tumors. To overcome these limitations, tumor-targeting, redox-activatable, and oxygen self-enriched theranostic nanoparticles are developed by synthesizing chlorin e6 (Ce6) conjugated hyaluronic acid (HA) with reducible disulfide bonds (HSC) and encapsulating perfluorohexane (PFH) within the nanoparticles (PFH@HSC). The fluorescence and phototoxicity of PFH@HSC nanoparticles are greatly inhibited by a self-quenching effect in an aqueous environment. However, after accumulating in tumors through passive and active tumor-targeting, PFH@HSC appear to be activated from “OFF” to “ON” in photoactivity by the redox-responsive destruction of the vehicle’s structure. In addition, PFH@HSC can load oxygen within lungs during blood circulation, and the oxygen dissolved in PFH is slowly released and diffuses over the entire tumor, finally resulting in remarkable tumor hypoxia relief and enhancement of PDT efficacy by generating more singlet oxygen. Taking advantage of the excellent imaging performance of Ce6, the tumor accumulation of PFH@HSC can be monitored by fluorescent and photoacoustic imaging after intravenous administration into tumor-bearing mice. This PFH@HSC nanoparticle might have good potential for dual imaging-guided PDT in hypoxic solid tumor treatment.
关键词： tumor hypoxia,hyaluronic acid nanoparticles,perfluorocarbon,redox-responsive,photodynamic therapy
更新于2025-11-19 16:46:39
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Hypoxia-Irrelevant Photonic Thermodynamic Cancer Nanomedicine
摘要： The hypoxic tumor microenvironment severely lowers the therapeutic efficacy of oxygen-dependent anticancer modalities because tumor hypoxia hinders the generation of toxic reactive oxygen species. Here we report a thermodynamic cancer-therapeutic modality that employs oxygen-irrelevant free radicals generated from thermo-labile initiators for inducing cancer-cell death. Free radical nanogenerator was engineered via direct growth of mesoporous silica layer onto the surface of two-dimensional Nb2C MXene nanosheets towards multifunctionality, where the mesopore provided the reservoirs for initiators and MXene core acted as the photonic-thermal trigger at near infrared-II biowindow (NIR-II). Upon illumination by a 1064 nm NIR-II laser, the photothermal-conversion effect of Nb2C MXene induced the fast release and quick decomposition of the encapsulated initiators (AIPH) to produce free radicals, which promoted cancer-cell apoptosis in both normoxic and hypoxic microenvironment. Systematic in vitro and in vivo evaluations have demonstrated the synergistic-therapeutic outcome of this intriguing photonic nanoplatform-enabled thermodynamic cancer therapy for completely eradicating the tumors without recurrence by NIR-II laser irradiation. This work pioneers the thermodynamic therapy for oxygen-independent cancer treatment by photonic triggering at NIR-II biowindow.
关键词： nanomedicine,thermodynamic therapy,photothermal effect,tumor hypoxia,free radicals
更新于2025-09-23 15:23:52
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Nanostars on Nanopipettes: A Raman Probe for Quantifying Oxygen Levels in Hypoxia in Single Cells and Tumors
摘要： Multiple sharp-edged gold nanostars were efficiently assembled on nanopipette tips by 3-aminopropyltrimethoxysilane (APTES) via an electrostatic interaction for a potent intracellular hypoxia-sensing Raman probe. Colloidal stability and surface immobilization was checked using scanning electron microscopy, light scattering and zeta potential measurements. Site-specific intracellular hypoxia levels can be estimated in vitro and in vivo using Raman lancets (RL). Distinct Raman spectral changes for the nitro-(NO2) functional group of the redox maker 4-nitrothiophenol (4NTP) can be quantified according to the intracellular oxygen (O2) contents, ranging from 1% to 10%. Facile removal of RL from cells can be achieved after a short measurement time. Redox potential changes in mitochondrial respiration could also be examined using serial injection of inhibitors. Three-dimensional (3D)-cultured cells and in vivo tests were used to validate our methods of measuring tumour hypoxia; potential applications were validated in terms of judging the aggressiveness of cancer cells by differentiating spectral changes between malignant and benign cells.
关键词： Cancer aggressiveness,Hypoxia,Surface enhanced resonance Raman,Intracellular redox potential,Nanopipette lancets
更新于2025-09-23 15:23:52
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Nanostars on Nanopipettes: A Raman Probe for Quantifying Oxygen Levels in Hypoxia in Single Cells and Tumors
摘要： Multiple sharp-edged gold nanostars were efficiently assembled on nanopipette tips by 3-aminopropyltrimethoxysilane (APTES) via an electrostatic interaction for a potent intracellular hypoxia-sensing Raman probe. Colloidal stability and surface immobilization was checked using scanning electron microscopy, light scattering and zeta potential measurements. Site-specific intracellular hypoxia levels can be estimated in vitro and in vivo using Raman lancets (RL). Distinct Raman spectral changes for the nitro-(NO2) functional group of the redox maker 4-nitrothiophenol (4NTP) can be quantified according to the intracellular oxygen (O2) contents, ranging from 1% to 10%. Facile removal of RL from cells can be achieved after a short measurement time. Redox potential changes in mitochondrial respiration could also be examined using serial injection of inhibitors. Three-dimensional (3D)-cultured cells and in vivo tests were used to validate our methods of measuring tumour hypoxia; potential applications were validated in terms of judging the aggressiveness of cancer cells by differentiating spectral changes between malignant and benign cells.
关键词： Hypoxia,Intracellular redox potential,Cancer aggressiveness,Nanopipette lancets,Surface enhanced resonance Raman
更新于2025-09-23 15:23:52
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In situ Determination of Nitrate and Hydrogen Sulfide in the Baltic Sea Using an Ultraviolet Spectrophotometer
摘要： Evaluating the health status of marine ecosystems becomes ever increasingly important especially against the backdrop of rising pressures from human activities. This is true especially for coastal seas such as the Baltic Sea that is surrounded by highly industrialized countries. Nutrients and pollutants such as nitrate and hydrogen sulfide, which have a major impact on ecosystem functioning, are two of several indicators for assessing the status of natural waters, and therefore key environmental of considerable interest. The frequency and the spatial coverage of the nitrate and hydrogen sulfide measurements are currently limited by the cost of the laboratory analysis and personnel. Optical in situ sensors can help to overcome this challenge by allowing reagentless and fast detection of dissolved chemical species. A chemical-free optical sensor has been used for direct and simultaneous measurements of both key parameters, and the results were compared with traditional methods. The data were collected during an observational program conducted in the Baltic Sea in February 2018. We used the OPUS UV spectral sensor, which was deployed for the first time in coastal waters, in combination with a deep-sea telemetry system to enable near-real time measurements during CTD profiling. Data processing was carried out using a multiple linear regression procedure. Measurements from both OPUS and on-board analysis were in good agreement. The results showed, that in situ UV-VIS spectrophotometry provides the capability to determine the concentration distributions of nitrate and hydrogen sulfide in the brackish waters of the Baltic Sea.
关键词： sulfide,Baltic Sea,monitoring,hypoxia,nutrients,UV-VIS spectrophotometry
更新于2025-09-23 15:22:29
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Quantitative photoacoustic imaging study of tumours in vivo: Baseline variations in quantitative measurements
摘要： Photoacoustic imaging (PAI) provides information on haemoglobin levels and blood oxygenation (sO2). To facilitate assessment of the variability in sO2 and haemoglobin in tumours, for example in response to therapies, the baseline variability of these parameters was evaluated in subcutaneous head and neck tumours in mice, using a PAI system (MSOTinVision-256TF). Tumours of anaesthetized animals (midazolam-fentanyl-medetomidine) were imaged for 75 min, in varying positions, and repeatedly over 6 days. An increasing linear trend for average tumoural haemoglobin and blood sO2 was observed, when imaging over 75 min. There were no significant differences in these temporal trends, when repositioning tumours. A negative correlation was found between the percent decrease in blood sO2 over 6 days and tumour growth rate. This paper shows the potential of PAI to provide baseline data for assessing the significance of intra- and inter-tumoural variations that may eventually have value for predicting and/or monitoring cancer treatment response.
关键词： Head and neck subcutaneous tumours,Hemoglobin,Pimonidazole,Blood sO2,Hypoxia,Photoacoustic imaging
更新于2025-09-23 15:22:29
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Smart NIR-Light-Mediated Nanotherapeutic Agents for Enhancing Tumor Accumulation and Overcoming Hypoxia in Synergistic Cancer Therapy
摘要： The efficacy of photodynamic therapy (PDT) still shows limited success in clinical application due to hypoxia in the solid tumor, low tumor accumulation and limited light penetration depth of photosensitizers (PS). The previously reported MnO2-based nanotherapeutic agents always required intratumoral injection or complex targeting modification process to improve the therapeutic efficacy. Herein, new MnO2-based nanotherapeutic agents (honeycomb MnO2/IR780/BSA nanoparticles, HMIB NPs) are designed and prepared to achieve excellent phototherapeutic performance characterized by NIR-light-mediation, deep diffusion via TME response and O2 self-supply. The ex vivo and in vivo NIR fluorescence imaging results demonstrate that the honeycomb nanostructure of HMIB NPs facilitates the high tumor accumulation of hydrophobic IR780 via enhanced permeability and retention (EPR) effect after intravenous injection. The immunofluorescence results demonstrate that the TME response of HMIB NPs not only provides O2 for relieving hypoxia but also reduces size for improving deep intratumoral diffusion. As a result, under the synergy of NIR fluorescence imaging, photothermal effect and PDT of IR780 with TME responsive size-change and O2 self-supply of honeycomb MnO2, the HMIB NPs have achieved all-in-one NIR fluorescence and photothermal dual-model imaging guided synergistic PDT/PTT under a single-wavelength NIR light irradiation.
关键词： nanotherapeutic agents,tumor microenvironment responsive degradation,photodynamic therapy,hypoxia,honeycomb manganese dioxide
更新于2025-09-23 15:22:29
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Response of Inner Retinal Oxygen Extraction Fraction to Light Flicker Under Normoxia and Hypoxia in Rat
摘要： PURPOSE. Oxygen extraction fraction (OEF), defined by the ratio of oxygen metabolism (MO2) to delivery (DO2), determines the level of compensation of MO2 by DO2. In the current study, we tested the hypothesis that inner retinal OEF remains unchanged during light flicker under systemic normoxia and hypoxia in rats due to the matching of MO2 and DO2. METHODS. Retinal vascular oxygen tension (PO2) measurements were obtained in 10 rats by phosphorescence lifetime imaging. Inner retinal OEF was derived from vascular PO2 based on Fick's principle. Measurements were obtained before and during light flicker under systemic normoxia and hypoxia. The effects of light flicker and systemic oxygenation on retinal vascular PO2 and OEF were determined by ANOVA. RESULTS. During light flicker, retinal venous PO2 decreased (P < 0.01, N = 10), while inner retinal OEF increased (P = 0.02). Under hypoxia, retinal arterial and venous PO2 decreased (P < 0.01), while OEF increased (P < 0.01). The interaction effect was not significant on OEF (P = 0.52), indicating the responses of OEF to light flicker were similar under normoxia and hypoxia. During light flicker, OEF increased from 0.46 ± 0.13 to 0.50 ± 0.11 under normoxia, while under hypoxia, OEF increased from 0.67 ± 0.16 to 0.74 ± 0.14. CONCLUSIONS. Inner retinal OEF increased during light flicker, indicating the relative change in DO2 is less than that in MO2 in rats under systemic normoxia and hypoxia. Inner retinal OEF is a potentially useful parameter for assessment of the relative changes of MO2 and DO2 under physiologic and pathologic conditions.
关键词： vascular oxygen tension,retina,oxygen extraction fraction,hypoxia,light flicker
更新于2025-09-23 15:22:29
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Photobiomodulation Preconditioning Prevents Cognitive Impairment in a Neonatal Rat Model of Hypoxia-ischemia
摘要： Neonatal hypoxia-ischemia (HI) injury caused by oxygen deprivation is the most common cause of mortality and severe neurologic deficits in neonates. The present work evaluated the preventative effect of photobiomodulation (PBM) preconditioning, and its underlying mechanism of action on brain damage in a HI model in neonatal rats. According to the optimal time response of ATP levels in brain samples removed from normal rats, a PBM preconditioning regimen (808 nm CW laser, 1 cm2 spot, 100 mW/cm2, 12 J/cm2) was delivered to the scalp 6 hours before HI. PBM preconditioning significantly attenuated cognitive impairment, volume shrinkage in the brain, neuron loss, dendritic and synaptic injury after HI. Further mechanistic investigation found that PBM preconditioning could restore HI-induced mitochondrial dynamics and inhibit mitochondrial fragmentation, followed by a robust suppression of cytochrome c release, and prevention of neuronal apoptosis by inhibition of caspase activation. Our work suggests that PBM preconditioning can attenuate HI-induced brain injury by maintaining mitochondrial dynamics and inhibiting the mitochondrial apoptotic pathway.
关键词： Hypoxia-ischemia,Mitochondria,Cognitive impairment,Neuroprotection,Photobiomodulation preconditioning
更新于2025-09-23 15:22:29