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Helicobacter pylori (H. pylori) infection presents increasing challenges to antibiotic therapies in limited penetration through gastric mucus, multi-drug resistance (MDR), biofilm formation, and intestinal microflora dysbiosis. To address these problems, herein, a mucus-penetrating phototherapeutic nanomedicine (RLs@T780TG) against MDR H. pylori infection is engineered. The RLs@T780TG is assembled with a near-infrared photosensitizer T780T-Gu and an anionic component rhamnolipids (RLs) for deep mucus penetration and light-induced anti-H. pylori performances. With optimized suitable size, hydrophilicity and weak negative surface, the RLs@T780TG can effectively penetrate through the gastric mucus layer and target the inflammatory site. Subsequently, under irradiation, the structure of RLs@T780TG is disrupted and facilitates the T780T-Gu releasing to target the H. pylori surface and ablate multi-drug resistant (MDR) H. pylori. In vivo, RLs@T780TG phototherapy exhibits impressive eradication against H. pylori. The gastric lesions are significantly alleviated and intestinal bacteria balance is less affected than antibiotic treatment. Summarily, this work provides a potential nanomedicine design to facilitate in vivo phototherapy in treatment of H. pylori infection.
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Infecções por Helicobacter , Helicobacter pylori , Muco , Helicobacter pylori/efeitos dos fármacos , Infecções por Helicobacter/tratamento farmacológico , Muco/metabolismo , Animais , Fototerapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Glicolipídeos/química , Glicolipídeos/farmacologia , Camundongos , Administração OralRESUMO
Helicobacter pylori (H. pylori) infection has been the leading cause of gastric cancer development. In recent years, the resistance of H. pylori against antibiotic treatment has been a great challenge for most countries worldwide. Since biofilm formation is one of the reasons for the antibiotic resistance of H. pylori, and phototherapy has emerged as a promisingly alternative antibacterial treatment, herein the bacteria-targeted near-infrared (NIR) photosensitizer (T780T-Gu) by combining positively-charged guanidinium (Gu) with an efficient phototherapeutic agent T780T is developed. The proposed molecule T780T-Gu exhibits synergistic photothermal therapy/photodynamic therapy effect against both H. pylori biofilms and multidrug-resistant (MDR) clinical strains. More importantly, the phototherapy mechanism of T780T-Gu acquired by the RNA-seq analysis indicates that structural deficiency as well as a decrease in metabolism and defense activity are the possible reasons for the efficient H. pylori phototherapy.
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Infecções por Helicobacter , Helicobacter pylori , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fototerapia , Biofilmes , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêuticoRESUMO
Extensive attention has been recently focused on designing signal adjustable biosensors. However, there are limited approaches available in this field. In this work, to visually track lysosomes with high contrast, we used the i-motif structure as a pH-responsive unit and proposed a novel strategy to regulate the fluorescence resonance energy transfer (FRET) response of the pH sensor. By simply splitting the i-motif into two parts and modulating the split parameters, we can tune the pH transition midpoint (pHt) from 5.71 to 6.81 and the signal-to-noise ratio (S/N) from 1.94 to 18.11. To facilitate the lysosome tracking, we combined the i-motif split design with tetrahedral DNA (Td). The obtained pH nanosensor (pH-Td) displays appropriate pHt (6.12) to trace lysosomes with high S/N (10.3). Benefited from the improved stability, the superior cell uptake and lysosomal location of pH-Td, the visualization of the distribution of lysosomes, the lysosome-mitochondria interaction, and the pH changes of lysosomes in response to different stimuli were successfully achieved in NIH 3T3 cells. We believe that the design concept of controlling the split sequence distance will provide a novel insight into the design of i-motif-based nanosensors and even inspire the construction of smart DNA nanodevices for sensing, disease diagnosis, and controllable drug delivery.
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Transferência Ressonante de Energia de Fluorescência , Corantes Fluorescentes , Animais , DNA , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Lisossomos , CamundongosRESUMO
Abbe diffraction limit has always been an important subject in conventional far-field focusing and imaging systems, where the resolution of an image is usually limited to 0.5λ/NA. Recently, the studies of the optical super-oscillation lens (SOL) enable us to break the limitation in both theory and practice successfully. Here a genetic algorithm was introduced to design the SOL phase more controllably and precisely obtain much better focusing such as the focal spot with 0.105λ/NA (or 79.0% minification) in the simulation and 65.5% minification in the experimental demonstration. This technique is of great significance in advanced optical lithography or biology microscopy, because it promises non-invasive unlabelled imaging from the far field.
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The spontaneous parametric down-conversion (SPDC) source of entangled-photon pairs is important for applications in the quantum information process and quantum communication, but suffers from scattering by sample defect and air impurity. Here, we proposed an alternative scheme to manipulate the scattered SPDC process, where only a spatial light modulator was used to control the incident wavefront. The scheme was experimentally tested and also applied on the manipulation of photon pairs through the SPDC process with spectral control. This work proved the feasibility of manipulating nonlinear signals at quantum level with feedback-based wavefront shaping and also indicated applications in long-distance quantum key distribution, quantum communications, and quantum imaging, especially in complex environments.
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Surface plasmon polariton (SPP) is an electromagnetic excitation with efficient spatial confinement and high local field intensity at a metal/dielectric interface, which has been widely applied in many fields such as nanophotonics, imaging, biosensing, nonlinear optics, and so on. However, the destructive interference, which arises from wavevector mismatching between the spatial components of incident light and SPP, limits the effective excitation of SPP. Here, we experimentally demonstrate the enhancement of SPP excitation via a feedback-based wavefront shaping method in the Kreschmann configuration. After optimizing the phase profile of the incident laser beam, the intensity is enhanced by a factor of 1.58 times even at the resonance angle of the fundamental mode Gaussian beam. Besides, the influences of different conditions for the enhancement of SPP excitation are also analyzed. This work provides a flexible and convenient method to further enhance the SPP excitation, and it may have the application of further enhancement of the interaction between SPP and other physical processes.
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Second-harmonic generation (SHG) is always a significant frequency conversion process in nonlinear optics for many great applications but can be limited when broadband spectral laser sources are involved, e.g., femtosecond pulses. The conversion efficiency can be high, but the spectral control is hard because of the phase-matching (PM) limitation. Recently, a random quasi-phase-matching (QPM) scheme was proposed to make use of highly nonlinear materials that are difficult to be phase matched under traditional configurations. The spectral control is even harder in anisotropic random materials, and the coherence is completely lost. Here, we proposed an approach to solve this problem by coherent light control via feedback-based wavefront shaping. We utilized this method for spectral control of broadband SHG, which can be efficient even in strongly scattering media. Randomly selected wavelengths in the broadband spectra were enhanced with a good selectivity, and the direction was also controlled in a three-dimensional (3D) configuration. This technique paves the way for convenient spatial and spectral control of both linear and nonlinear emissions and a local enhancement of their conversion efficiency, indicating great progress in both random and ultrafast nonlinear optics.
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Nonlinear optical wave mixing is a widely used method to produce light with new frequencies that has a significant impact on laser technology and optical imaging. The most important figure of merit in wave-mixing processes, i.e., high conversion efficiency, is always required in laser applications. We demonstrate a method to recover high conversion efficiency of second harmonic generation in a BaMgF4 single crystal with weakly scattering defects via feedback-based wavefront shaping under birefringent phase-matching condition. By optimizing the fundamental wavefront, a typical second harmonic output with an enhancement factor of 1.14 and a corresponding recovery efficiency of 86.3% is displayed. This investigation may modify the wide understanding of scattering in crystals and provide an avenue to recover the nonlinear optical conversion efficiency in crystals with various defects without special fabrications.
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Scattering has usually been considered detrimental for optical focusing or imaging. Recently, more and more research has shown that strongly scattering materials can be utilized to focus coherent light by controlling or shaping the incident light. Here, purposeful focusing of second-harmonic waves, which are generated and scattered from nonlinear turbid media via feedback-based wavefront shaping, is presented. This Letter shows a flexible manipulation of both disordered linear and nonlinear scattering signals, indicating more controllable degrees of freedom for the description of turbid media. This technique also provides a possible way to an efficient transmission of nonlinear signal at a desired location in the form of a focal point or other patterns. With the combination of random nonlinear optics and wavefront shaping methods, more interesting applications can be expected in the future, such as nonlinear transmission matrix, multi-frequency imaging, and phase-matching-free nonlinear optics.
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To date, research on abalone adhesion has primarily analyzed the organism's adhesion to smooth surfaces, with few studies on adhesion to non-smooth surfaces. The present study examined the surface morphology of the abalone's abdominal foot, followed by measuring the adhesive force of the abalone on a smooth force measuring plate and five force measuring plates with different surface morphologies. Next, the adhesion mechanism of the abdominal foot was analyzed. The findings indicated that the abdominal foot of the abalone features numerous stripe-shaped folds on its surface. The adhesion of the abalone to a fine frosted glass plate, a coarse frosted glass plate, and a quadrangular conical glass plate was not significantly different from that on a smooth glass plate. However, the organism's adhesion to a small lattice pit glass plate and block pattern glass plate was significantly different. The abalone could effectively adhere to the surface of the block pattern glass plate using the elasticity of its abdominal foot during adhesion but experienced difficulty in completely adhering to the surface of the quadrangular conical glass plate. The abdominal foot used its elasticity to form an independent sucker system with each small lattice pit, significantly improving adhesion to the small lattice pit glass plate. The elasticity of the abalone's abdominal foot created difficulty in handling slight morphological size changes in roughness, resulting in no significant differences in its adhesion to the smooth glass plate.
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Pyroptosis has been reported to improve the antitumor effect by evoking a more intense immune response and a therapeutic effect. For phototherapy, several photosensitizers have been found to initiate pyroptosis. However, the effect of pyroptosis associated with apoptosis in enhancing the antitumor therapy needs sufficient characterization, especially under long-term treatment. As a NIR photosensitizer, heptamethine cyanines have been discovered for anticancer phototherapy for deep tissue penetration and inherent tumor-targeted capability. However, they are not quite stable for long-term performance. To investigate the effect of pyroptosis along with apoptosis on the anticancer immune responses and phototherapy, here, we chemically modulate the cyanine IR780 to regulate hydrophobicity, stability, and intracellular targeting. Two photosensitizers, T780T-TPP and T780T-TPP-C12, were finally optimized and showed excellent photostability with high photothermal conversion efficiency. Although the cellular uptake of the two molecules was both mediated by OATP transporters, T780T-TPP induced tumor cell death via pyroptosis and apoptosis and accumulated in tumor accumulation, while T780T-TPP-C12 was prone to accumulate in the liver. Ultimately, via one injection-multiple irradiation treatment protocol, T780T-TPP displayed a significant antitumor effect, even against the growth of large tumors (200 mm3).
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Nanopartículas , Neoplasias , Humanos , Piroptose , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fototerapia/métodos , Neoplasias/tratamento farmacológico , Apoptose , Mitocôndrias , Nanopartículas/química , Linhagem Celular TumoralRESUMO
Helicobacter pylori (H. pylori) infection has increasingly been a serious problem worldwide. The H. pylori infection can result in a series of stomach diseases including gastric carcinoma. There are two specific virulence genes (cagA and vacA) of H. pylori that are closely related to the occurrence of gastric cancer, and the common molecular detection methods (PCR, qPCR) are not suitable for high-screening test due to the requirement of expensive instruments and well-trained personals. Herein, we develop a rapid visual assay based on loop-mediated isothermal amplification (LAMP) for detecting H. pylori and its major virulence genes (cagA, vacAs1 and vacAm1) to guide clinical treatment for H. pylori infection. In this research, a fluorescent LAMP assay was established by optimizing the indicator of MnCl2-Calcein, so that the resulted color and fluorescence changes could be utilized to perform the visual detection for H. pylori and its virulence genes with high sensitivity (10-3 ng/µL). The proposed LAMP assay is simple, fast (30 min) and capable in providing more sensitive results than traditional methods in the test of 46 clinical biopsy samples. By detecting the three virulence genes together, we can profile the infection risk of the patients, and discuss the correlation among the genes. Moreover, the method could be used to diagnose virulently infected individuals and benefit the eradication of H. pylori in early warning for gastric cancer.
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Carcinoma , Gastrite , Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Humanos , Virulência/genética , Proteínas de Bactérias/genética , Antígenos de Bactérias/genética , Helicobacter pylori/genética , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Genótipo , Gastrite/genética , Gastrite/patologia , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/patologiaRESUMO
With the rapid development of nanotechnology, researchers have designed a variety of intelligent nanodelivery systems to enhance tumor targeting of anticancer drugs. However, increased tumor accumulation does not indicate deeper penetration in the tumor tissue, without which the tumor cells in the core area cannot be sufficiently killed. Herein, we develop a size-controllable nanoparticle system for deep-penetrating cancer therapy, which will be programmably disassembled with the decrease of the pH from the normal tissue to the tumor microenvironment and to the intracellular area. The integrated nanoparticle is composed of a gold nanoparticle (GNP, â¼30 nm) and a tetrahedral DNA nanostructure (TDN, â¼25 nm) loaded with doxorubicin (DOX). Initially, the nanoparticles maintain a larger size (â¼100 nm) to accumulate in the tumor through the enhanced permeability and retention effect. At a pH of about 6.5 at the tumor microenvironment, with the linkage of DNA sequences converting into a triplex structure, the TDNs detach from the GNP and penetrate deeply into the tumor interstitium and then are internalized into the cells. Finally, in acidic lysosomes with pH 5.0, the TDNs release DOX by forming an i-motif structure. This nanosmart delivery system thus shows effective deep penetration into the tumor core with good antitumor efficacy and satisfactory biocompatibility and provides new insights into the development of intelligent nanosystems for anti-cancer treatment.
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Nanopartículas Metálicas , Nanopartículas , Neoplasias , Linhagem Celular Tumoral , DNA , Doxorrubicina/química , Sistemas de Liberação de Medicamentos , Ouro/química , Humanos , Concentração de Íons de Hidrogênio , Nanopartículas Metálicas/química , Nanopartículas/química , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Microambiente TumoralRESUMO
Reliable and accurate glucose detection in biological samples is of great importance in clinical diagnosis and medical research. Chemical probes are advantageous in simple operation and flexible design, especially for the development of fluorescent probes. Anthracene-based diboronic acid (P-DBA) has shown potential in glucose probing because of its high sensitivity. However, poor solubility limits its applications in aqueous media. In this work, we systemically modify P-DBA by introducing fluoro (F-), chloro (Cl-), methoxyl (MeO-), or cyano (CN-) substituents. Among these probes, the cyano-substituted probe (CN-DBA) displays the highest glucose-binding constant (6489.5 M-1, 33% MeOH). More importantly, it shows good water solubility in the aqueous solution (0.5% MeOH), with ultrasensitive recognition with glucose (LOD = 1.51 µM) and robust sensing from pH 6.0 to 9.0. Based on these features, the CN-DBA is finally applied to detect glucose in cell lysates and plasma, with satisfactory recovery and precision. These results demonstrate that CN-DBA could serve as an accurate, sensitive fluorescent probe for glucose assays in biological samples.
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Corantes Fluorescentes , Glucose , Solubilidade , ÁguaRESUMO
As a photosensitizer with effective photothermal (PTT) and photodynamic (PDT) response, IR780 has been widely explored as promising cancer phototheranostic molecule. However, the systematic administration of IR780 usually suffers from poor water solubility and low photostability, so that it cannot be administrated by parenteral route. In this study, we design a tetrahedral DNA (Td)-based nanosystem to load IR780 (IR780@Td) via electrostatic interaction and π-π stacking. After encapsulation, the water solubility and photostability of IR780 have been greatly improved, and the IR780@Td shows an appropriate nanoformulated size (224 nm) to facilitate hyperthermia-mediated tumor targeting by EPR effect. The nanostructure of Td is proved to be crucial for the proper size and good stability of IR780@Td nanoformulation for in vivo application. The in vitro and ex vivo PTT/PDT efficiencies of IR780 are improved in IR780@Td group. In the tumor-bearing mice, the accumulation of IR780 in tumor site is significantly high in IR780@Td group. Under near-infrared laser irradiation, the intravenous administration of IR780@Td promotes the tumor imaging and enhances anti-tumor effect than IR780 treatment. In summary, the proposed strategy shows promising effect in facilitating intravenous injection of IR780 and enhancing the phototheranostic efficacy for cancer treatment.
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Hipertermia Induzida , Nanopartículas , Nanoestruturas , Neoplasias , Fotoquimioterapia , Animais , Linhagem Celular Tumoral , DNA , Indóis , Camundongos , Neoplasias/tratamento farmacológicoRESUMO
Near-infrared (NIR) fluorescent probes can deeply penetrate through tissues with little damage. To facilitate image-guided theranostics, researchers usually apply a desired amount of photosensitizers to achieve effective photothermal responses. However, these probes could easily suffer from low photostability and aggregated-caused quenching effect in high concentrations. In this paper, the rational incorporation of an aggregated-induced emission (AIE) unit into the structure of heptamethine cyanine IR-780 is reported. Using tetraphenylethene (TPE) as an AIE core, we synthesize three TPE-modified IR-780 probes (IR-780 AIEgens) via different linkages. The IR-780 derivatives all show enhanced AIE features, in which the probe with an ether linkage (IR780-O-TPE) is superior in rapid cell uptake, high targeting capacity, and good photostability. Moreover, IR780-O-TPE exhibits the strongest cytotoxicity to HeLa cells (IC50 = 3.3 µM). The three IR-780 derivatives displayed a photothermal response in a concentration-dependent manner, in which IR-780 AIEgens are more cytotoxic than IR-780, with IC50 of 0.3 µM under 808 nm laser irradiation. In tumor-bearing mice, the optimal probe IR780-O-TPE also showed a more effective photothermal response than IR-780. By illustrating the relationship between aggregation state with photophysical properties, cell imaging, and cytotoxicity, this work is helpful in modulating NIR-based photosensitizers into AIE features for efficient image-guided theranostics.