RESUMO
BACKGROUND: Radiodynamic therapy (RDT) holds the potential to overcome the shallow tissue penetration issue associated with conventional photodynamic therapy (PDT). To this end, complex and sometimes toxic scintillator-photosensitizer nanoconjugates are often used, posing barriers for large-scale manufacturing and regulatory approval. METHODS: Herein, we report a streamlined RDT strategy based on CsI(Na)@MgO nanoparticles and 5-aminolevulinic acid (5-ALA). 5-ALA is a clinically approved photosensitizer, converted to protoporphyrin IX (PpIX) in cancer cells' mitochondria. CsI(Na)@MgO nanoparticles produce strong ~ 410 nm X-ray luminescence, which matches the Soret band of PpIX. We hypothesize that the CsI(Na)@MgO-and-5-ALA combination can mediate RDT wherein mitochondria-targeted PDT synergizes with DNA-targeted irradiation for efficient cancer cell killing. Because scintillator nanoparticles and photosensitizer are administered separately, the approach forgoes issues such as self-quenching or uncontrolled release of photosensitizers. RESULTS: When tested in vitro with 4T1 cells, the CsI(Na)@MgO and 5-ALA combination elevated radiation-induced reactive oxygen species (ROS), enhancing damages to mitochondria, DNA, and lipids, eventually reducing cell proliferation and clonogenicity. When tested in vivo in 4T1 models, RDT with the CsI(Na)@MgO and 5-ALA combination significantly improved tumor suppression and animal survival relative to radiation therapy (RT) alone. After treatment, the scintillator nanoparticles, made of low-toxic alkali and halide elements, were efficiently excreted, causing no detectable harm to the hosts. CONCLUSIONS: Our studies show that separately administering CsI(Na)@MgO nanoparticles and 5-ALA represents a safe and streamlined RDT approach with potential in clinical translation.
Assuntos
Nanopartículas , Fotoquimioterapia , Ácido Aminolevulínico/farmacologia , Animais , Linhagem Celular Tumoral , Óxido de Magnésio , Nanopartículas/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêuticoRESUMO
BACKGROUND: Photodynamic therapy (PDT) may elicit antitumor immune response in addition to killing cancer cells. However, PDT as a monotherapy often fails to induce a strong immunity. Immune checkpoint inhibitors, which selectively block regulatory axes, may be used in combination with PDT to improve treatment outcomes. Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme and an important meditator of tumor immune escape. Combination therapy with PDT and IDO-targeted immune checkpoint blockage is promising but has been seldom been explored. METHODS: Herein we report a composite nanoparticle that allows for simultaneous delivery of photosensitizer and IDO inhibitor. Briefly, we separately load ZnF16Pc, a photosensitizer, and NLG919, an indoleamine 2,3-dioxygenase (IDO) inhibitor, into ferritin and poly(lactide-co-glycolic)-block-poly(ethylene glycol) (PEG-PLGA) nanoparticles; we then conjugate these two compartments to form a composite nanoparticle referred to as PPF NPs. We tested combination treatment with PPF NPs first in vitro and then in vivo in B16F10-tumor bearing C57/BL6 mice. RESULTS: Our results showed that PPF NPs can efficiently encapsulate both ZnF16Pc and NLG919. In vivo studies found that the combination treatment led to significantly improved tumor suppression and animal survival. Moreover, the treatment increased tumor infiltration of CD8+ T cells, while reducing frequencies of MDSCs and Tregs. 30% of the animals showed complete tumor eradication, and they successfully rejected a second tumor inoculation. Overall, our studies introduce a unique composite nanoplatform that allows for co-delivery of photosensitizer and IDO inhibitor with minimal inter-species interference, which is ideal for combination therapy.
Assuntos
Sistemas de Liberação de Medicamentos/métodos , Imunoterapia/métodos , Indolamina-Pirrol 2,3,-Dioxigenase/efeitos dos fármacos , Nanoconjugados/uso terapêutico , Nanopartículas/uso terapêutico , Fotoquimioterapia/métodos , Animais , Linfócitos T CD8-Positivos , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Inibidores Enzimáticos/farmacologia , Ferritinas , Humanos , Imidazóis , Isoindóis , Camundongos , Células Supressoras Mieloides , Nanoconjugados/química , Nanopartículas/química , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêuticoRESUMO
Based on the micro-hyperspectral imaging technique, spherical engineered microplastic (polyethylene, 10-45 µm) and microalgae (Isochrysis galbana) (4-7 µm) were identified. In transmittance mode of MHSI, micro image cubes from 400 to 1000 nm were obtained from slides containing MP and MA in thin seawater. Classifiers like Support Vector Machine (SVM(Radial Basis Function (RBF))), Least Squares Support Vector Machine (LSSVM(RBF)), k-Nearest Neighbors, etc. were adopted and compared to classify MP and MA. In order to expand the imaging range of micro imaging, image stitching technology was adopted. In allusion to the stitched image cube, SVM(RBF) is suggested for the identification of MA and MP, with recall and precision > 0.86. The above results demonstrate that the MHSI is a promising technique, which can detect MPs with particle size Limit of Detection of 10-45 µm, and it is potential to further expand this LOD.
Assuntos
Haptófitas , Microalgas , Imageamento Hiperespectral , Microplásticos , PlásticosRESUMO
An ultra-broadband metamaterial absorber, consisting of 2D SiO2-Ti square bilayer grating on SiO2 film and Ti substrate, is proposed and designed by rigorous coupled wave analysis (RCWA) and genetic algorithm (GA) methods. The optimized structure shows an average absorption of 98.3% in the wavelength range of 300 nm to 2100 nm. Moreover, the metamaterial absorber is polarization-independent and also insensitive to incidence angle for both TM- and TE-polarized waves. The physical mechanisms responsible for nearly perfect broadband absorption, including the Wood's anomaly (WA), cavity resonance (CR), surface plasmon polaritons (SPPs) and the resonance of magnetic polaritons (MPs), have been analyzed clearly by finite-difference time-domain (FDTD) method and the inductor-capacitor (LC) circuit model. Overall, the proposed metamaterial absorber is a promising candidate in solar applications.
RESUMO
High-Z nanoparticles have emerged as a novel type of radiosensitizers due to their relatively large X-ray cross-section and ability to enhance radical production under irradiation. Recently, CaWO4 nanoparticles have been prepared and their potential as a radiosensitizer has been demonstrated. Herein, we investigated BaWO4 nanoparticles as a novel type of alkaline-earth metal tungstate radiosensitizer for radiotherapy (RT). We synthesized BaWO4 nanoparticles using hydrothermal reaction and coated them with polyvinylpyrrolidone (PVP). We found that BaWO4 nanoparticles could more efficiently enhance hydroxyl radical production under irradiation than CaWO4 nanoparticles. When tested in vitro, BaWO4 nanoparticles showed lower toxicity than CaWO4 nanoparticles in the absence of irradiation, but induced more significant oxidative stress under irradiation. When tested in vivo, BaWO4 nanoparticles led to more efficient tumor inhibition without causing systemic toxicity. Overall, our results suggest that BaWO4 nanoparticles can efficiently enhance RT and hold great potential as a novel type of radiosensitizing agent.
Assuntos
Bário/química , Nanopartículas Metálicas/química , Radiossensibilizantes/química , Compostos de Tungstênio/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Radical Hidroxila/química , Camundongos Endogâmicos BALB C , Oxigênio Singlete/químicaRESUMO
This paper investigated the use of spectra and multispectral images for on-site visualized classification of transparent hazards and noxious substances (HNS), such as benzene, xylene, and palm oil, floating on a water surface with the potential use for rapid classification of multiple HNS during a leak accident. Partial least-squares discrimination analysis (PLS-DA) and least-squares support vector machine (LS-SVM) models achieved a classification accuracy of 100% for spectral reflectance (325-900 nm) and multispectral image at nine wavelengths. Wavelength division and selection were applied for spectra and spectral images, respectively, to reduce the difficulty in data collection and to simplify the redundant bands. This was followed by PLS-DA and LS-SVM modeling. The LS-SVM model based on the least wavelengths (365, 410, 450, and 850 nm) of multispectral images was suggested as the most effective method for on-site visualized classification of transparent HNS on a water surface.
RESUMO
Underwater spectral imaging is a promising method for mapping, classification and health monitoring of coral reefs and seafloor inhabitants. However, the spectrum of light is distorted during the underwater imaging process due to wavelength-dependent attenuation by the water. This paper presents a model-based method that accurately restores brightness of underwater spectral images captured with narrowband filters. A model is built for narrowband underwater spectral imaging. The model structure is derived from physical principles, representing the absorption, scattering and refraction by water and the optical properties of narrowband filters, lenses and image sensors. The model coefficients are calibrated based on spectral images captured underwater and in air. With the imaging model available, energy loss due to water attenuation is restored for images captured at different underwater distances. An experimental setup is built and experiments are carried out to verify the proposed method. Underwater images captured within an underwater distance of 260 cm are restored and compared with those in air. Results show that the relative restoration error is 3.58% on average for the test images, thus proving the accuracy of the proposed method.
RESUMO
Turbidity measurement is important for water quality assessment, food safety, medicine, ocean monitoring, etc. In this paper, a method that accurately estimates the turbidity over a wide range is proposed, where the turbidity of the sample is represented as a weighted ratio of the scattered light intensities at a series of angles. An improvement in the accuracy is achieved by expanding the structure of the ratio function, thus adding more flexibility to the turbidity-intensity fitting. Experiments have been carried out with an 850 nm laser and a power meter fixed on a turntable to measure the light intensity at different angles. The results show that the relative estimation error of the proposed method is 0.58% on average for a four-angle intensity combination for all test samples with a turbidity ranging from 160 NTU to 4000 NTU.
RESUMO
Calcium nanoparticles have been investigated for applications, such as drug and gene delivery. Additionally, Ca2+ serves as a crucial second messenger in the activation of immune cells. However, few studies have systematically studied the effects of calcium nanoparticles on the calcium levels and functions within immune cells. In this study, we explore the potential of calcium nanoparticles as a vehicle to deliver calcium into the cytosol of dendritic cells (DCs) and influence their functions. We synthesized calcium hydroxide nanoparticles, coated them with a layer of silica to prevent rapid degradation, and further conjugated them with anti-CD205 antibodies to achieve targeted delivery to DCs. Our results indicate that these nanoparticles can efficiently enter DCs and release calcium ions in a controlled manner. This elevation in cytosolic calcium activates both the NFAT and NF-κB pathways, in turn promoting the expression of costimulatory molecules, antigen-presenting molecules, and pro-inflammatory cytokines. In mouse tumor models, the calcium nanoparticles enhanced the antitumor immune response and augmented the efficacy of both radiotherapy and chemotherapy without introducing additional toxicity. Our study introduces a safe nanoparticle immunomodulator with potential widespread applications in cancer therapy.
Assuntos
Cálcio , Nanopartículas , Animais , Camundongos , Cálcio/metabolismo , Citosol/metabolismo , Citocinas/metabolismo , Células Dendríticas , Imunoterapia/métodosRESUMO
In the underwater environment, conventional hyperspectral imagers for imaging target scenes usually require stable carrying platforms for completing push sweep or complex optical components for beam splitting in long gaze imaging, which limits the system's efficiency. In this paper, we put forward a novel underwater hyperspectral imaging (UHI) system inspired by the visual features of typical cephalopods. We designed a visual bionic lens which enlarged the chromatic blur effect to further ensure that the system obtained blur images with high discrimination of different bands. Then, chromatic blur datasets were collected underwater to complete network training for hyperspectral image reconstruction. Based on the trained model, our system only required three frames of chromatic blur images as input to effectively reconstruct spectral images of 30 bands in the working light range from 430 nm to 720 nm. The results showed that the proposed hyperspectral imaging system exhibited good spectral imaging potential. Moreover, compared with the traditional gaze imaging, when obtaining similar hyperspectral images, the data sampling rate in the proposed system was reduced by 90%, and the exposure time of required images was only about 2.1 ms, reduced by 99.98%, which can greatly expand its practical application range. This experimental study illustrates the potential of chromatic blur vision for UHI, which can provide rapid response in the recognition task of some underwater dynamic scenarios.
Assuntos
Diagnóstico por Imagem , Imageamento Hiperespectral , Processamento de Imagem Assistida por ComputadorRESUMO
Iodine has shown promise in enhancing radiotherapy. However, conventional iodine compounds show fast clearance and low retention inside cancer cells, limiting their application as a radiosensitizer. Herein, we synthesize poly(maleic anhydride-alt-1-octadecene) coated KI nanoparticles (PMAO-KI NPs) and evaluate their potential for enhancing radiotherapy. Owing to the polymer coating, the KI core of PMAO-KI NPs is not instantly dissolved in aqueous solutions but slowly degraded, allowing for controlled release of iodide (I-). I- is transported into cells via the sodium iodide symporter (NIS), which is upregulated in breast cancer cells. Our results show that PMAO-KI NPs can enhance radiation-induced production of reactive oxygen species such as hydroxyl radicals. When tested in vitro with MCF-7 cells, PMAO-KI NPs promote radiation-induced DNA double-strand breaks and lipid peroxidation, causing a drop in cancer cell viability and reproductivity. When tested in MCF-7 bearing mice, PMAO-KI NPs show significant radiosensitizing effects, leading to complete tumor eradication in 80% of the treated animals without inducing additional toxicity. Overall, our strategy exploits electrolyte nanoparticles to deliver iodide into cancer cells through NIS, thus promoting radiotherapy against breast cancer.
Assuntos
Nanopartículas , Neoplasias , Animais , Camundongos , Iodetos/metabolismo , Iodeto de Potássio , Linhagem Celular Tumoral , Tretinoína/farmacologiaRESUMO
The spatial distribution detection and characterization of multi-adsorption layers, biomembranes, and cells are important techniques to study biomolecular properties and mechanisms. Using the surface plasmon resonance (SPR) technology, we investigated the spatial characteristics, penetration mechanism, and detection depth of the interaction between evanescent waves and a complex medium. In addition, parameters correlated with the axial spatial distribution were analyzed. We found that the spatial refractive-index distribution of an axial layered model has a unique correlation with the following three characteristic parameters: resonance angle at different wavelengths, first-derivative extreme-point of the angular spectrum, and effective refractive index. A new layer-analysis, based on wavelength-scanning angle interrogation (WSAI), was introduced to enable refractive-index measurements in an axial spatial medium. This new method extends the detection capabilities of SPR sensors and provides a more accurate analysis method for interaction events within an evanescent field.
RESUMO
The automatic identification (location, segmentation, and classification) by UAV- based optical imaging of spills of transparent floating Hazardous and Noxious Substances (HNS) benefits the on-site response to spill incidents, but it is also challenging. With a focus on the on-site optical imaging of HNS, this study explores the potential of single spectral imaging for HNS identification using the Faster R-CNN architecture. Images at 365â¯nm (narrow UV band), blue channel images (visible broadband of â¼400-600â¯nm), and RGB images of typical HNS (benzene, xylene, and palm oil) in different scenarios were studied with and without Faster R-CNN. Faster R-CNN was applied to locate and classify the HNS spills. The segmentation using Faster R-CNN-based methods and the original masking methods, including Otsu, Max entropy, and the local fuzzy thresholding method (LFTM), were investigated to explore the optimal wavelength and corresponding image processing method for the optical imaging of HNS. We also compared the classification and segmentation results of this study with our previously published studies on multispectral and whole spectral images. The results demonstrated that single spectral UV imaging at 365â¯nm combined with Faster R-CNN has great potential for the automatic identification of transparent HNS floating on the surface of the water. RGB images and images using Faster R-CNN in the blue channel are capable of HNS segmentation.
Assuntos
Substâncias Perigosas/análise , Hidrocarbonetos/análise , Redes Neurais de Computação , Poluição Química da Água/análise , Poluição por Petróleo/análise , Análise EspectralRESUMO
Triglycerides are clinically important marker for atherosclerosis, heart disease and hypertension. Here, a platform for detecting triglycerides in whole blood directly was developed based on hemocompatible É-polylysine-heparin microparticles. The obtained products of É-polylysine-heparin microparticles were characterized by fourier transform infrared (FT-IR) spectra, transmission electron microscopy (TEM) and ζ-potential. Moreover, the blood compatibility of É-polylysine-heparin microparticles was characterized by in vitro coagulation tests, hemolysis assay and whole blood adhesion tests. Considering of uniform particle size, good dispersibility and moderate long-term anticoagulation capability of the microparticles, a Lipase-(É-polylysine-heparin)-glassy carbon electrode (GCE) was constructed to detect triglycerides. The proposed biosensor had good electrocatalytic activity towards triglycerides, in which case the sensitivity was 0.40µAmg-1dLcm-2 and the detection limit was 4.67mgdL-1 (S/N = 3). Meanwhile, the Lipase-(É-polylysine-heparin)-GCE electrode had strong anti-interference ability as well as a long shelf-life. Moreover, for the detection of triglycerides in whole blood directly, the detection limit was as low as 5.18mgdL-1. The new constructed platform is suitable for detecting triglycerides in whole blood directly, which provides new analytical systems for clinical illness diagnosis.
Assuntos
Técnicas Biossensoriais , Micropartículas Derivadas de Células/química , Heparina/análogos & derivados , Polilisina/análogos & derivados , Triglicerídeos/isolamento & purificação , Heparina/química , Humanos , Limite de Detecção , Lipase/química , Microscopia Eletrônica de Transmissão , Polilisina/química , Espectroscopia de Infravermelho com Transformada de Fourier , Triglicerídeos/sangueRESUMO
Mesoporous silica has been developed for the modification of titanium surfaces that are used as implant materials. Yet, the traditional modification methods failed to effectively construct mesoporous silica on the titanium surface evenly and firmly, in which the interaction between mesoporous silica and titanium was mainly physical. Here, in situ growth of mesoporous silica on a titanium surface was performed using a simple evaporation-induced self-assembly strategy. Meantime, in situ introduction of drugs (heparin and vancomycin) to mesoporous silica was also adopted to improve the drug-loading amount. Both the above-mentioned processes were completed at the same time. Transmission electron microscopy, N2 adsorption-desorption isotherms, Fourier transform infrared spectroscopy, scanning electron microscopy, and water contact angle measurements were used to characterize the structure of the mesoporous silica film. Results indicated that the mesoporous silica film that in situ grew on the titanium surface was smooth, thin, transparent, and stable. Cytotoxicity, proliferation performance of osteoblast cells, and in vitro and in vivo studies of the antibacterial activity of the coating were tested. This is the first study to modify the titanium surface by the in situ growth of a mesoporous silica coating with two kinds of drugs. The stability of the mesoporous silica coating can be attributed to the chemical bonding between dopamine and silicon hydroxyl of the mesoporous silica coating, and the smooth surface of mesoporous silica is a result of the method of in situ growth. The large amount of drug-loading also could be ascribed to the in situ introduction of drugs during the synthetic process. The strategy proposed in this work will bring more possibilities for the preparation of advanced functional materials based on the combination of mesoporous structure and metallic materials.
Assuntos
Titânio/química , Adsorção , Osteoblastos , Porosidade , Dióxido de Silício , Propriedades de SuperfícieRESUMO
Accurate values of tumor markers in blood play an especially important role in the diagnosis of illness. Here, based on the combination of three techniques include anticoagulant technology, nanotechnology and biosensing technology, a sensitive label-free immunosensor with anti-biofouling electrode for detection α-Fetoprotein (AFP) in whole blood was developed by anticoagulating magnetic nanoparticles. The obtained products of Fe3O4-É-PL-Hep nanoparticles were characterized by fourier transform infrared (FT-IR) spectra, transmission electron microscopy (TEM), ζ-potential and vibrating sample magnetometry (VSM). Moreover, the blood compatibility of anticoagulating magnetic nanoparticles was characterized by in vitro coagulation tests, hemolysis assay and whole blood adhesion tests. Combining the anticoagulant property of heparin (Hep) and the good magnetism of Fe3O4, the Fe3O4-É-PL-Hep nanoparticles could improve not only the anti-biofouling property of the electrode surface when they contact with whole blood, but also the stability and reproducibility of the proposed immunosensor. Thus, the prepared anticoagulating magnetic nanoparticles modified immunosensor for the detection of AFP showed excellent electrochemical properties with a wide concentration range from 0.1 to 100ng/mL and a low detection limit of 0.072ng/mL. Furthermore, five blood samples were assayed using the developed immunosensor. The results showed satisfactory accuracy with low relative errors. It indicated that our developed immunoassay was competitive and could be potentially used for the detection of whole blood samples directly.