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Compressed ultrafast photography (CUP) can capture irreversible or difficult-to-repeat dynamic scenes at the imaging speed of more than one billion frames per second, which is obtained by compressive sensing-based image reconstruction from a compressed 2D image through the discretization of detector pixels. However, an excessively high data compression ratio in CUP severely degrades the image reconstruction quality, thereby restricting its ability to observe ultrafast dynamic scenes with complex spatial structures. To address this issue, a discrete illumination-based CUP (DI-CUP) with high fidelity is reported. In DI-CUP, the dynamic scenes are loaded into an ultrashort laser pulse train with controllable sub-pulse number and time interval, thus the data compression ratio, as well as the overlap between adjacent frames, is greatly decreased and flexibly controlled through the discretization of dynamic scenes based on laser pulse train illumination, and high-fidelity image reconstruction can be realized within the same observation time window. Furthermore, the superior performance of DI-CUP is verified by observing femtosecond laser-induced ablation dynamics and plasma channel evolution, which are hardly resolved in the spatial structures using conventional CUP. It is anticipated that DI-CUP will be widely and dependably used in the real-time observations of various ultrafast dynamics.
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Ultrafast imaging can capture the dynamic scenes with a nanosecond and even femtosecond temporal resolution. Complementarily, phase imaging can provide the morphology, refractive index, or thickness information that intensity imaging cannot represent. Therefore, it is important to realize the simultaneous ultrafast intensity and phase imaging for achieving as much information as possible in the detection of ultrafast dynamic scenes. Here, we report a single-shot intensity- and phase-sensitive compressive sensing-based coherent modulation ultrafast imaging technique, shortened as CS-CMUI, which integrates coherent modulation imaging, compressive imaging, and streak imaging. We theoretically demonstrate through numerical simulations that CS-CMUI can obtain both the intensity and phase information of the dynamic scenes with ultrahigh fidelity. Furthermore, we experimentally build a CS-CMUI system and successfully measure the intensity and phase evolution of a multimode Q-switched laser pulse and the dynamical behavior of laser ablation on an indium tin oxide thin film. It is anticipated that CS-CMUI enables a profound comprehension of ultrafast phenomena and promotes the advancement of various practical applications, which will have substantial impact on fundamental and applied sciences.
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Cancer cells have a strategically optimized metabolism and tumor microenvironment for rapid proliferation and growth. Increasing research efforts have been focused on developing therapeutic agents that specifically target the metabolism of cancer cells. In this work, we prepared 1-methyl-4-phenylpyridinium-functionalized Ir(iii) complexes that selectively localize in the mitochondria and generate singlet oxygen and superoxide anion radicals upon two-photon irradiation. The generation of this oxidative stress leads to the disruption of the mitochondrial respiratory chain and therefore the disturbance of mitochondrial oxidative phosphorylation and glycolysis metabolisms, triggering cell death by combining immunogenic cell death and ferritinophagy. To the best of our knowledge, this latter is reported for the first time in the context of photodynamic therapy (PDT). To provide cancer selectivity, the best compound of this work was encapsulated within exosomes to form tumor-targeted nanoparticles. Treatment of the primary tumor of mice with two-photon irradiation (720 nm) 24 h after injection of the nanoparticles in the tail vein stops the primary tumor progression and almost completely inhibits the growth of distant tumors that were not irradiated. Our compound is a promising photosensitizer that efficiently disrupts the mitochondrial respiratory chain and induces ferritinophagy-mediated long-term immunotherapy.
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Compressed ultrafast photography (CUP) is a novel two-dimensional (2D) imaging technique to capture ultrafast dynamic scenes. Effective image reconstruction is essential in CUP systems. However, existing reconstruction algorithms mostly rely on image priors and complex parameter spaces. Therefore, in general, they are time-consuming and result in poor imaging quality, which limits their practical applications. In this paper, we propose a novel reconstruction algorithm, to the best of our knowledge, named plug-in-plug-fast deep video denoising net-total variation (PnP-TV-FastDVDnet), which exploits an image's spatial features and correlation features in the temporal dimension. Therefore, it offers higher-quality images than those in previously reported methods. First, we built a forward mathematical model of the CUP, and the closed-form solution of the three suboptimization problems was derived according to plug-in and plug-out frames. Secondly, we used an advanced video denoising algorithm based on a neural network named FastDVDnet to solve the denoising problem. The peak signal-to-noise ratio (PSNR) and structural similarity index measure (SSIM) are improved on actual CUP data compared with traditional algorithms. On benchmark and real CUP datasets, the proposed method shows the comparable visual results while reducing the running time by 96% over state-of-the-art algorithms.
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Melanoma represents the most fatal form of skin cancer due to its resistance mechanisms and high capacity for the development of metastases. Among other medicinal techniques, photodynamic therapy is receiving increasing attention. Despite promising results, the application of photodynamic therapy is inherently limited due to interference from melanin, poor tissue penetration of photosensitizers, low loading into drug delivery systems, and a lack of tumor selectivity. To overcome these limitations, herein, the coordination-driven assembly of Ir(III) complex photosensitizers with Fe(III) ions into nanopolymers for combined photodynamic therapy and chemodynamic therapy is reported. While remaining stable under physiological conditions, the nanopolymers dissociated in the tumor microenvironment. Upon exposure to light, the Ir(III) complexes produced singlet oxygen and superoxide anion radicals, inducing cell death by apoptosis and autophagy. The Fe(III) ions were reduced to Fe(II) upon depletion of glutathione and reduction of the GPX4 levels, triggering cell death by ferroptosis. To provide tumor selectivity, the nanopolymers were further camouflaged with exosomes. The generated nanoparticles were found to eradicate a melanoma tumor as well as inhibit the formation of metastases inside a mouse model.
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Exossomos , Ferroptose , Melanoma , Neoplasias , Fotoquimioterapia , Animais , Camundongos , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Irídio , Compostos Férricos/uso terapêutico , Neoplasias/tratamento farmacológico , Fotoquimioterapia/métodos , Melanoma/tratamento farmacológico , Apoptose , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
Metal nitrides show excellent photothermal stability and conversion properties, which have the potential for photothermal therapy (PTT) for cancer. Photoacoustic imaging (PAI) is a new non-invasive and non-ionizing biomedical imaging method that can provide real-time guidance for precise cancer treatment. In this work, we develop polyvinylpyrrolidone-functionalized tantalum nitride nanoparticles (defined as TaN-PVP NPs) for PAI-guided PTT of cancer in the second near-infrared (NIR-II) window. The TaN-PVP NPs are obtained by ultrasonic crushing of massive tantalum nitride and further modification by PVP to obtain good dispersion in water. Due to their good absorbance in the NIR-II window, TaN-PVP NPs with good biocompatibility have obvious photothermal conversion performance, realizing efficient tumor elimination by PTT in the NIR-II window. Meanwhile, the excellent PAI and photothermal imaging (PTI) capabilities of TaN-PVP NPs are able to provide monitoring and guidance for the treatment process. These results indicate that TaN-PVP NPs are qualified for cancer photothermal theranostics.
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Hyperspectrally compressed ultrafast photography (HCUP) based on compressed sensing and time- and spectrum-to-space mappings can simultaneously realize the temporal and spectral imaging of non-repeatable or difficult-to-repeat transient events with a passive manner in single exposure. HCUP possesses an incredibly high frame rate of tens of trillions of frames per second and a sequence depth of several hundred, and therefore plays a revolutionary role in single-shot ultrafast optical imaging. However, due to ultra-high data compression ratios induced by the extremely large sequence depth, as well as limited fidelities of traditional algorithms over the image reconstruction process, HCUP suffers from a poor image reconstruction quality and fails to capture fine structures in complex transient scenes. To overcome these restrictions, we report a flexible image reconstruction algorithm based on a total variation (TV) and cascaded denoisers (CD) for HCUP, named the TV-CD algorithm. The TV-CD algorithm applies the TV denoising model cascaded with several advanced deep learning-based denoising models in the iterative plug-and-play alternating direction method of multipliers framework, which not only preserves the image smoothness with TV, but also obtains more priori with CD. Therefore, it solves the common sparsity representation problem in local similarity and motion compensation. Both the simulation and experimental results show that the proposed TV-CD algorithm can effectively improve the image reconstruction accuracy and quality of HCUP, and may further promote the practical applications of HCUP in capturing high-dimensional complex physical, chemical and biological ultrafast dynamic scenes.
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Being capable of passively capturing transient scenes occurring in picoseconds and even shorter time with an extremely large sequence depth in a snapshot, compressed ultrafast photography (CUP) has aroused tremendous attention in ultrafast optical imaging. However, the high compression ratio induced by large sequence depth brings the problem of low image quality in image reconstruction, preventing CUP from observing transient scenes with fine spatial information. To overcome these restrictions, we propose an efficient image reconstruction algorithm with multi-scale (MS) weighted denoising based on the plug-and-play (PnP) based alternating direction method of multipliers (ADMM) framework for multi-channel coupled CUP (MC-CUP), named the MCMS-PnP algorithm. By removing non-Gaussian distributed noise using weighted MS denoising during each iteration of the ADMM, and adaptively adjusting the weights via sufficiently exploiting the coupling information among different acquisition channels collected by MC-CUP, a synergistic combination of hardware and algorithm can be realized to significantly improve the quality of image reconstruction. Both simulation and experimental results demonstrate that the proposed adaptive MCMS-PnP algorithm can effectively improve the accuracy and quality of reconstructed images in MC-CUP, and extend the detectable range of CUP to transient scenes with fine structures.
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Advances in mechanistic understanding of integrin-mediated adhesion highlight the importance of precise control of ligand presentation in directing cell migration. Top-down nanopatterning limited the spatial presentation to sub-micron placing restrictions on both fundamental study and biomedical applications. To break the constraint, here we propose a bottom-up nanofabrication strategy to enhance the spatial resolution to the molecular level using simple formulation that is applicable as treatment agent. Via self-assembly and co-assembly, precise control of ligand presentation is succeeded by varying the proportions of assembling ligand and nonfunctional peptide. Assembled nanofilaments fulfill multi-functions exerting enhancement to suppression effect on cell migration with tunable amplitudes. Self-assembled nanofilaments possessing by far the highest ligand density prevent integrin/actin disassembly at cell rear, which expands the perspective of ligand-density-dependent-modulation, revealing valuable inputs to therapeutic innovations in tumor metastasis.
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Integrinas , Adesão Celular/fisiologia , Movimento Celular/fisiologia , Integrinas/metabolismo , Ligantes , Ligação ProteicaRESUMO
Live cell imaging of lysosome positioning and motility is critical to studying lysosome status and function for pharmacological interventions. To create a super stable lysosomal probe for long-term live cell imaging, we have designed and synthesized an aromatic-peptide-conjugated cyclometalated iridium(III) complex that emits light via π-π stacking oriented self-assembly in water at extremely low concentration. Through endocytic trafficking, self-assemblies are transformed from nanoparticles into sturdily packed networks that are stabilized in lysosomal acidic environment. Upon short time/low dose treatment of the iridium complex at passage 0, live cell lysosomal tracking is applicable beyond the 14th passage of cells with high labelling rate and a mild decline in luminescence intensity. The illuminated lysosomes are trackable using super-resolution imaging to study their response to cellular processes.
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Complexos de Coordenação/química , Corantes Fluorescentes/química , Irídio/química , Lisossomos/metabolismo , Rastreamento de Células , Dimerização , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Conformação Molecular , Nanopartículas/química , Imagem Óptica , Peptídeos/química , Espectrometria de FluorescênciaRESUMO
Compared to 2PE (two-photon excitation) microscopy, 3PE microscopy has superior spatial resolution, deeper tissue penetration, and less defocused interference. The design of suitable agents with a large Stokes shift, good three-photon absorption (3PA), subcellular targeting, and fluorescence lifetime imaging (FLIM) properties, is challenging. Now, two IrIII complexes (3PAIr1 and 3PAIr2) were developed as efficient three-photon phosphorescence (3PP) agents. Calculations reveal that the introduction of a new group to the molecular scaffold confers a quadruple promotion in three-photon transition probability. Confocal and lifetime imaging of mitochondria using IrIII complexes as 3PP agents is shown. The complexes exhibit low working concentration (50â nm), fast uptake (5â min), and low threshold for three-photon excitation power (0.5â mW at 980â nm). The impressive tissue penetration depth (ca. 450â µm) allowed the 3D imaging and reconstruction of brain vasculature from a living specimen.
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Complexos de Coordenação/química , Irídio/química , Imagem Óptica/métodos , Animais , Células HeLa , Humanos , Camundongos , Fótons , Peixe-ZebraRESUMO
Herein, we present a series of dual-targeted ruthenium-glucose conjugates that can function as two-photon absorption (TPA) PDT agents to effectively destroy tumors by preferentially targeting both tumor cells and mitochondria. The in vivo experiments revealed an excellent tumor inhibitory efficiency of the dual-targeted TPA PSs.
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Glucose/uso terapêutico , Mitocôndrias/metabolismo , Neoplasias/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Rutênio/uso terapêutico , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Glucose/farmacologia , Humanos , Luz , Camundongos Endogâmicos BALB C , Neoplasias/metabolismo , Neoplasias/patologia , Fármacos Fotossensibilizantes/farmacologia , Rutênio/farmacologia , Carga Tumoral/efeitos dos fármacosRESUMO
Malignant brain cancer remains challenging in treatment due to the highly invasive quality of gliomas. Inspired by the upregulated expression of integrin ß1 subunits in tumors, we designed and synthesized an integrin-targeting self-assembling ligand based on a laminin-derived peptide that selectively forms nanofibrous microdomains on the apical membrane of glioma cells, inhibiting their migration and invasion.
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Glioma , Movimento Celular , Glioma/tratamento farmacológico , Humanos , Integrina beta1 , Integrinas , LigantesRESUMO
Platinum-resistant cancer cells are sensitive to changes in the levels of reactive oxidative species (ROS). Herein, we design a biotin-modified Ru(ii) complex as a photosensitizer (denoted as Ru-Biotin). Ru-Biotin can selectively target cancer cells and produce vast amounts of singlet oxygen under two-photon excitation at 820 nm leading to cell apoptosis. Ru-Biotin is therefore an excellent candidate to overcome platinum resistance via two-photon photodynamic therapy.
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Antineoplásicos/farmacologia , Biotina/análogos & derivados , Biotina/farmacologia , Complexos de Coordenação/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Rutênio/química , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/efeitos da radiação , Apoptose/efeitos dos fármacos , Biotina/síntese química , Biotina/efeitos da radiação , Caspase 3/metabolismo , Caspase 7/metabolismo , Linhagem Celular Tumoral , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Complexos de Coordenação/efeitos da radiação , Humanos , Raios Infravermelhos , Fotoquimioterapia/métodos , Fótons , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/efeitos da radiação , Oxigênio Singlete/metabolismoRESUMO
The endoplasmic reticulum (ER) is an indispensable organelle that undertakes the synthesis and export of proteins and membrane lipids. Subtle interferences of the ER redox signaling pathway are very likely to cause ER-stress induced apoptosis. In view of this, we herein present a series of ER-targeted Ir(iii) complexes (Ir1-Ir3) as photodynamic therapy (PDT) photosensitizers with a gradually extended conjugation area in the main ligand, and study the correlation between the conjugation area and PDT performance. The results showed that all of these complexes can accumulate in the ER and effectively induce cell apoptosis after PDT therapeutics (405 nm, 6 J cm-2) by an ER stress mechanism, and both their singlet oxygen quantum yields and cytotoxicities increase as the conjugation area extends. All complexes showed PDT efficacy towards different cancer cell lines. Among them, Ir2 exhibited the highest PI value (94.3) against A549 cells with an IC50 down to 0.65 µM. In addition, the post PDT ER-stress induced apoptosis along with the efflux of Ca2+ from the ER system in A549 cells in a short period of time (45-90 min) with the pretreatment of Ir2 was demonstrated. All of these results indicate the promising potential of Ir2 as an effective PDT photosensitizer.
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In this paper, the DNA interaction properties of four Ru(ii) polypyridyl complexes, [Ru(bpy)2(pip)]2+ (1), bpy = 2,2'-bipyridine, pip = 2-phenyl-imidazo[4,5-f][1,10]phenanthroline, [Ru(bpy)2(nip)]2+ (2), nip = 2-naphthyl-imidazo[4,5-f][1,10]phenanthroline, [Ru(bpy)2(aip)]2+ (3), aip = 2-(9-anthryl)-imidazo[4,5-f][1,10]phenanthroline and [Ru(bpy)2(pyip)]2+ (4), pyip = 2-(1-pyrenyl)-imidazo[4,5-f][1,10]phenanthroline, were investigated by spectral titration. The intensity increases in the MLCT band of the complexes and the decrease in absorption due to the DNA secondary structure was attributed to DNA condensation by these complexes. The DNA condensing behavior of these complexes was investigated in more detail by gel electrophoresis (GAR), dynamic light scattering (DLS), zeta potential, atomic force microscopy (AFM), and transmission electron microscopy (TEM). The results suggest that the concentration of the complex plays a critical role in its DNA intercalating and DNA condensing behavior. Meanwhile, the aryl units in the ligands of complex 1-4 also have a large effect on their interactions with DNA.
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Combining luminescent transition metal complex with super-resolution microscopy is an excellent strategy for the long-term visualization of the dynamics of subcellular structures in living cells. However, it remains unclear whether iridium(III) complexes are applicable for a particular type of super-resolution technique, structured illumination microscopy (SIM), to image subcellular structures. Herein, an iridium(III) dye, to track mitochondrial dynamics in living cells under SIM is described. The dye demonstrates excellent specificity and photostability and satisfactory cell permeability. While using SIM to image mitochondria, an ≈80 nm resolution is achieved that allows the clear observation of the structure of mitochondrial cristae. The dye is used to monitor and quantify mitochondrial dynamics relative to lysosomes, including fusion involved in mitophagy, and newly discovered mitochondria-lysosome contact (MLC) under different conditions. The MLC remains intact and fusion vanishes when five receptors, p62, NDP52, OPTN, NBR1, and TAX1BP1, are knocked out, suggesting that these two processes are independent.
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Irídio/química , Lisossomos/química , Membranas Mitocondriais/química , Mitofagia/fisiologiaRESUMO
Oncosis is a non-apoptotic form of programmed cell death (PCD), which differs from apoptosis in both morphological changes and inner pathways, and might hold the key to defeating a major obstacle in cancer therapy - drug-resistance, which is often a result of the intrinsic apoptosis resistance of tumours. However, despite the fact that the term "oncosis" was coined and used much earlier than apoptosis, little effort has been made to discover new drugs which can initiate this form of cell death, in comparison to drugs inducing apoptosis or any other type of PCD. So herein, we present the synthesis of a series of mitochondria-targeting cyclometalated Ir(iii) complexes, which activated the oncosis-specific protein porimin and calpain in cisplatin-resistant cell line A549R, and determined their cytotoxicity against a wide range of drug-resistant cancer types. To the best of our knowledge, these complexes are the very first metallo-components to induce oncosis in drug-resistant cancer cells.
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In this work, it was found that DNA can undergo B-Z transformational changes and compaction in the presence of DNA intercalators such as ruthenium(II) polypyridyl complexes. The link between B-Z transition and condensation is weak but can be strengthened under certain circumstances with slight alterations to the structures of the ruthenium(II) complexes. Here, following on from previous research, this work reports a series of ruthenium(II) complexes with imidazophenanthroline ligands, which vary in size and planarity. The complexes exhibit distinct effects on DNA structures, ranging from little impact to the transformation of DNA secondary structures to the formation of higher-order DNA structures. Further studies on DNA morphological changes induced by chiral ruthenium(II) complexes are observed by atomic force microscopy and transmission electron microscopy.