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A nano-complex system to overcome antagonistic photo-chemo combination cancer therapy
摘要： Photo-Chemo combination therapy has been intensively investigated for treatment of cancers, especially multidrug resistance cancer. However, antagonistic interactions between chemo-drugs and photosensitizers are frequently reported, and drugs doses and treatment sequences have been changed to overcome the problems. We observed the antagonistic effect by a decrease in singlet oxygen generation from the photosensitizer when Dox was in close physical proximity. To control the distance between Dox and the photosensitizer, we developed a novel pH-sensitive poly ionomer complex system composed of PEG-PLL(-g-Ce6) [Chlorin e6 grafted poly(ethylene glycol)-poly(L-lysine)] and PEG-PLL(-g-DMA)-PLA [2,3-dimethylmaleic anhydride grafted poly(ethylene glycol)-poly(L-lysine)-poly(lactic acid)] and evaluated this system with regard to singlet oxygen generation and antiproliferative activity against MCF-7/Dox cells. Enhanced singlet oxygen generation and antiproliferative activities were observed in vitro and in vivo for the poly ionomer complex system compared to PEG-PLL(-g-Ce6)-PLA/Dox due to the change in distance between Dox and Ce6 in the PIC system under acidic conditions. Our results highlight the importance of interactions between co-loaded drugs in combination therapy, and provide new insights into design principles for tailor-made nanomedicine platforms.
关键词： pH sensitive,chlorin e6,photo-chemo combination therapy,MDR,doxorubicin,synergism
更新于2025-11-21 11:01:37
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Multi-point Gaussian States, Quadratic–Exponential Cost Functionals, and Large Deviations Estimates for Linear Quantum Stochastic Systems
摘要： This paper is concerned with risk-sensitive performance analysis for linear quantum stochastic systems interacting with external bosonic fields. We consider a cost functional in the form of the exponential moment of the integral of a quadratic polynomial of the system variables over a bounded time interval. Such functionals are related to more conservative behaviour and robustness of systems with respect to statistical uncertainty, which makes the challenging problems of their computation and minimization practically important. To this end, we obtain an integro-differential equation for the time evolution of the quadratic–exponential functional, which is different from the original quantum risk-sensitive performance criterion employed previously for measurement-based quantum control and filtering problems. Using multi-point Gaussian quantum states for the past history of the system variables and their first four moments, we discuss a quartic approximation of the cost functional and its infinite-horizon asymptotic behaviour. The computation of the asymptotic growth rate of this approximation is reduced to solving two algebraic Lyapunov equations. Further approximations of the cost functional, based on higher-order cumulants and their growth rates, are applied to large deviations estimates in the form of upper bounds for tail distributions. We discuss an auxiliary classical Gaussian–Markov diffusion process in a complex Euclidean space which reproduces the quantum system variables at the level of covariances but has different fourth-order cumulants, thus showing that the risk-sensitive criteria are not reducible to quadratic–exponential moments of classical Gaussian processes. The results of the paper are illustrated by a numerical example and may find applications to coherent quantum risk-sensitive control problems, where the plant and controller form a fully quantum closed-loop system, and other settings with nonquadratic cost functionals.
关键词： Linear quantum stochastic system,Gaussian quantum state,Risk-sensitive quantum control
更新于2025-09-23 15:23:52
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PEGylated doxorubicin cloaked nano-graphene oxide for dual-responsive photochemical therapy
摘要： Graphene oxide (GO) own huge surface area and high drug loading capacity for aromatic molecules, such as doxorubicin (DOX). However, its biocompatibility is poor and it might agglomerate in physiological condition. Chemical modification of GO with hydrophilic polymer, especially PEGylation, was a common method to improve its biocompatibility. But the chemical modification of GO was complicated, and its drug loading capacity might be reduced because of the occupation of its functional groups. In this study, DOX-PEG polymers with different PEG molecular weight were synthesized to modify nano graphene oxide (NGO) to simultaneously realize the solubilization of NGO and the high loading capacity of DOX. The result showed that the drug release of NGO@DOX-PEG was pH sensitive. NIR irradiation could augment the drug release, cellular uptake, cytotoxicity and nuclear translocation of nanodrugs. Among the three kinds of nanodrugs, NGO@DOX-PEG5K was superior to others. It suggested that after conjugating with PEG, the bond between DOX-PEG and NGO was weakened, which resulted in a better drug release and treatment effect. In summary, the NIR and pH dual-responsive NGO@DOX-PEG nanodrugs were developed by noncovalent modification, and it demonstrated excellent biocompatibility and photochemical therapeutic effect, presenting a promising candidate for antitumor therapy, especially NGO@DOX-PEG5K.
关键词： Nano-drug Delivery System,pH sensitive,Nano-Graphene Oxide,photochemical therapy,Doxorubicin
更新于2025-09-23 15:23:52
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Multi-arm polymers prepared by atom transfer radical polymerization (ATRP) and their electrospun films as oxygen sensors and pressure sensitive paints
摘要： New oxygen and pressure sensitive paints (PSPs) with four-arm polymeric structures were prepared by using a kind of controlled living polymerizations - atom transfer radical polymerization (ATRP). The polymers composing of poly(isobutyl methacrylate)-co-poly(trifluoroethyl methacrylate)s (PolyIBMA-co-PolyTFEM)s act as the matrices for the platinum porphyrin-based phosphorescence probes, which were copolymerized in the matrices. The polymers were characterized by using 1H-NMR, 19F-NMR, and GPC to demonstrate their successful preparation. The influence of polymer structures on sensing activity including the sensitivity and response time to oxygen and/or pressure was investigated. Results showed that copolymers with suitable compositions (herein P3) can have highest sensitivity. Polymer structure's influence on response time to oxygen was also investigated. For increasing the polymer's surface area for further improving sensing sensitivity, electrospinning method was used for preparing films with micro-spherical or fibrous structures. The morphologies of electrospinning coated films were observed by SEM. Results showed that electrospinning coated films can respond much better to oxygen and pressure than their corresponding sprayed plates. This is the first time to apply the controlled living polymerization approach to prepare PSPs with multi-arm structures, which will broaden the PSP functional materials' design strategy.
关键词： oxygen sensing,pressure sensitive paints,electrospinning,multi-arm polymers,atom transfer radical polymerization
更新于2025-09-23 15:23:52
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Analysis of Golgi pH in CHO cells using ratiometric pH-sensitive fluorescent proteins
摘要： Acidic Golgi pH plays an important role in protein glycosylation, one of the critical quality attributes of therapeutic proteins. To determine the intracellular Golgi pH during culture, stable CHO cell clones expressing pHluorin2, a ratiometric pH-sensitive fluorescent protein (FP), in the cis- and trans-Golgi, were constructed by fusing pHluorin2 with specific targeting proteins, acetylglucosaminyltransferase and galactosyltransferase, respectively. Stable CHO cell clones expressing pHluorin2 in cytoplasm were also constructed. The subcellular localization of FPs was confirmed by immunofluorescence analysis. Live-cell imaging revealed that the intracellular pH of clones expressing the ratiometric pH-sensitive FPs converged to a specific pH range (cis-Golgi: 6.4 – 6.5, trans-Golgi: 5.9 – 6.0, and cytoplasm: 7.1 – 7.2). The intracellular pH was successfully evaluated in various culture conditions. Although culture pH was maintained at 7.2 in a bioreactor, the Golgi pH increased with culture time. Elevated ammonia concentration and osmolality were partially responsible for the increased Golgi pH during bioreactor cultures. Taken together, the application of ratiometric pH-sensitive FPs in monitoring the Golgi pH of CHO cells during culture provides a new perspective to improve protein glycosylation through intracellular pH control.
关键词： cis-Golgi,trans-Golgi,ratiometric-pH sensitive protein,CHO cells,intracellular pH
更新于2025-09-23 15:23:52
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Probing Polarity and Heterogeneity of Lipid Droplets in Live Cells Using a Push–Pull Fluorophore
摘要： Lipid droplets (LDs) are organelles composed of a lipid core surrounded by a phospholipid monolayer. Lately, LDs attracted a considerable attention due to recent studies demonstrating their role in a variety of physiological processes as well as diseases. Herein we synthesized a push-pull molecule named DAF (Dimethyl Aniline Furaldehyde) that possesses a strong positive solvatochromism in emission of 119 nm from toluene to methanol. Its impressive fluorogenic properties from water to oil (2000-fold) as well as its high quantum yields (up to 0.97) led us to investigate its ability to sense the distribution of polarity in live cells by fluorescence ratiometric imaging. When added to live cells and excited at 405 nm, DAF immediately and brightly stain lipid droplets using a blue channel (410-500 nm) and cytoplasm in a red channel (500-600 nm). DAF also proved to be compatible with fixation thus allowing 3D imaging of LDs in their cytoplasm environment. Taking advantage of DAF emission in two distinct channels, ratiometric imaging was successfully performed and led to the polarity mapping of the cell unraveling some heterogeneity in polarity within LDs of the same cell.
关键词： Environment Sensitive Fluorescent Probe,Lipid Droplets,Ratiometric Imaging,Multicolor Fluorescent imaging
更新于2025-09-23 15:23:52
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Measurement of proton quenching in a LAB-based liquid scintillator
摘要： In this paper, we propose a mathematical model to evaluate the transmission of Tuberculosis with drug-resistant strains and with drug-sensitive strains. Based on the epidemic data from Chinese Center for Disease Control and Prevention, we first estimate the values of parameters in the model. Then the basic reproduction number of TB infection in the mainland China is calculated to be 1.0558. Since the basic reproduction number is greater than 1, Tuberculosis spreads as an endemic in mainland China. Through our investigations, the basic reproduction number associated with drug-sensitive strains is less than 1, but the number of individuals infected by drug-resistant strains will still increase quickly, thus the epidemic is not under control. Moreover, increasing the vaccination coverage rate for newborns is not always beneficial for controlling TB prevalence in China. Whether vaccination effect is positive or negative depends on the relapse rate from the recovered state to the infected state. In summary, improving sanitation conditions, introducing efficient measures to detect the disease, and keeping the public informed about how to lower the chance of being infected and the current epidemic situation are essential in slowing down or eliminating Tuberculosis transmission.
关键词： Tuberculosis Transmission,Drug-Sensitive Strain,The Basic Reproduction Number,Drug-Resistant Strain,Least-Square Method
更新于2025-09-23 15:23:52
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Highly Sensitive Polarization Photodetection Using a Pseudo-One-Dimensional Nb <sub/> (1– <i>x</i> ) </sub> Ti <sub/><i>x</i> </sub> S <sub/>3</sub> Alloy
摘要： Low-symmetry layered two-dimensional (2D) materials with strong in-plane optical anisotropy can potentially be applied for polarization photodetection. This is especially true for those 2D materials with a direct bandgap, who can efficiently absorb light with specific axial polarization. However, discovering such new anisotropic 2D materials with direct band structure is still extremely challenging. Here, we fabricate a photodetector using a pseudo-one-dimensional (pseudo-1D) Nb(1-x)TixS3 alloy device, and demonstrate that it is highly sensitive to the polarized light due to the strong in-plane optical anisotropy and direct bandgap of the alloy by combining the angle-resolved polarization Raman spectroscopy (ARPRS), azimuth-dependent reflectance difference microscopy (ADRDM), polarization-dependent absorption spectroscopy (PDAS), and hybrid functional theory calculations. As a consequence, the polarization photodetector of the Nb(1-x)TixS3 alloy shows a large photocurrent anisotropic ratio and a high photoresponse. The choice of low-symmetry layered pseudo-1D Nb(1-x)TixS3 alloy in polarization photodetection might open up new functionalities for novel optoelectronic device applications.
关键词： low-symmetry structure,in-plane optical anisotropy,pseudo-one-dimensional materials,Nb(1-x)TixS3 ternary alloy,polarization-sensitive photodetector
更新于2025-09-23 15:23:52
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[IEEE 2018 IEEE International Conference on Electrical Engineering and Photonics (EExPolytech) - Saint Petersburg, Russia (2018.10.22-2018.10.23)] 2018 IEEE International Conference on Electrical Engineering and Photonics (EExPolytech) - Study of Oxyfluoride Glasses with Silver Molecular Clusters for Application in Sensoric and Optoelectronics
摘要： Temperature sensitivity of Oxyfluoride glasses with molecular silver clusters and samarium ions were studied. The experimental procedure for obtaining luminescence spectra at various temperatures is described. The perspective of using oxyfluoride glasses in fiber-optic temperature sensors is considered.
关键词： sensitive element,luminescence,Fiber-optical temperature sensor,oxyfluoride glass,spectrum,molecular clusters of silver
更新于2025-09-23 15:23:52
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Multiphysics Simulation of Biosensors Involving 3D Biological Reaction-Diffusion Phenomena in a Standard Circuit EDA Environment
摘要： The topic of this paper is the development of biological models for 3D reaction–diffusion phenomena that can be used in any circuit electronic design automation environment for the simulation of biosensors. Biological systems that involve such 3D phenomena are described by partial differential equations. Our approach consists in discretizing these equations according to the finite-difference method and converting the resulting ordinary differential equations into an assembly of elementary electronic equivalent circuits that are directly simulated with SPICE. The main interest of this approach is the ability to couple such models with third-party SPICE models of electronic circuits, sensors, and transducers, i.e., models from any physical domain ruled by Kirchhoff laws, allowing modeling and simulation of any multi-physics systems in a conventional circuit design environment, here CADENCE. The tool is validated on simple problems for which analytical solutions are known. Then, the interest of the approach is illustrated on the study of a biosensor.
关键词： reaction-diffusion,Biosensor,virtual prototyping,biochemical reaction,ion-sensitive FET
更新于2025-09-23 15:22:29