Self‐Assembly of an Amphiphilic Janus Camptothecin–Floxuridine Conjugate into Liposome‐Like Nanocapsules for More Efficacious Combination Chemotherapy in Cancer

The combination of camptothecin (CPT) and fluoropyrimidine derivatives acts synergistically at a 1:1 molar ratio. Practically, the greatest challenge is the development of a single liposomal formulation that can both encapsulate and maintain this drug combination at an exact 1:1 ratio to achieve coordinated pharmacokinetics. Consequently, a new type of liposome‐like nanocapsule (NC) is developed from a highly symmetric Janus camptothecin–floxuridine conjugate (JCFC) amphiphile, which is synthesized by coupling two hydrophobic CPT molecules and two hydrophilic floxuridine (FUDR) molecules to multivalent pentaerythritol via a hydrolyzable ester linkage. JCFC NCs possess remarkably high drug‐loading contents, and no premature release because of the highly stable co‐delivery of the drug combination without the need for any carrier. It is shown that JCFC NCs consistently provide synergy and avoid antagonism in a broad panel of tumor cell lines. In vivo delivery of JCFC NCs leads to longer blood retention half‐life, higher tumorous accumulation and cellular uptake of drugs, and greatly enhanced efficacy in murine tumor models compared to CPT, FUDR, and CPT + FUDR. This liposomal strategy can be extended to other hydrophilic and hydrophobic anticancer drugs that are coupled to pentaerythritol to self‐assemble into nanocapsules for drug self‐delivery, pointing to potential clinical translation in near future.     

A Highly Entangled Polymeric Nanoconstruct Assembled by siRNA and its Reduction‐Triggered siRNA Release for Gene Silencing

A nanoconstruct (NC) is developed from a biocompatible natural polymer and siRNA conjugates to deliver small interfering RNA (siRNA) target‐specifically without cationic condensation reagents. This study reports a novel siRNA‐mediated cross‐linked NC produced by hybridizing two complementary single‐stranded siRNAs that are conjugated to the polymer dextran via a disulfide linkage. The reducible disulfide bond between the siRNA and polymer allow siRNA release from the NC in the reducible cytoplasmic region after the NC enters the cell. In addition, when the NC contains the prostate‐carcinoma‐binding peptide aptamer DUP‐1, it can selectively deliver siRNA into prostate cancer cells of the PC‐3 lines; thus, the newly formulated NC has reduced the cytotoxicity and improved the efficacy of target‐specific siRNA delivery. Moreover, this new concept of NCs using biocompatible siRNA and a neutral polymer may provide insightful knowledge for future directions for designing NCs for stimuli‐responsive and advanced target‐specific siRNA delivery.     

螺旋CT的应用及优势

本文介绍了螺旋CT的引进情况,阐述了螺旋CT的原理和在应用中的良好表现,并把螺旋CT与普通CT、多层螺旋CT与单层螺旋CT分别作了比较,优劣非常明显。     

螺旋CT的应用及优势

本文介绍了螺旋CT的引进情况，阐述了螺旋CT的原理和在应用中的良好表现，并把螺旋CT与普通CT、多层螺旋CT与单层螺旋CT分别作了比较，优劣非常明显。     

Synthesis and Assembly of Click‐Nucleic‐Acid‐Containing PEG–PLGA Nanoparticles for DNA Delivery

Co‐delivery of both chemotherapy drugs and siRNA from a single delivery vehicle can have a significant impact on cancer therapy due to the potential for overcoming issues such as drug resistance. However, the inherent chemical differences between charged nucleic acids and hydrophobic drugs have hindered entrapment of both components within a single carrier. While poly(ethylene glycol)‐block‐poly(lactic‐co‐glycolic acid) (PEG–PLGA) copolymers have been used successfully for targeted delivery of chemotherapy drugs, loading of DNA or RNA has been poor. It is demonstrated that significant amounts of DNA can be encapsulated within PLGA‐containing nanoparticles through the use of a new synthetic DNA analog, click nucleic acids (CNAs). First, triblock copolymers of PEG‐CNA‐PLGA are synthesized and then formulated into polymer nanoparticles from oil‐in‐water emulsions. The CNA‐containing particles show high encapsulation of DNA complementary to the CNA sequence, whereas PEG‐PLGA alone shows minimal DNA loading, and non‐complementary DNA strands do not get encapsulated within the PEG‐CNA‐PLGA nanoparticles. Furthermore, the dye pyrene can be successfully co‐loaded with DNA and lastly, a complex, larger DNA sequence that contains an overhang complementary to the CNA can also be encapsulated, demonstrating the potential utility of the CNA‐containing particles as carriers for chemotherapy agents and gene silencers.     

Synchrotron‐Based Micro‐CT and Refraction‐Enhanced Micro‐CT for Non‐Destructive Materials Characterisation

X‐ray computed tomography is an important tool for non‐destructively evaluating the 3‐D microstructure of modern materials. To resolve material structures in the micrometer range and below, high brilliance synchrotron radiation has to be used. The Federal Institute for Materials Research and Testing (BAM) has built up an imaging setup for micro‐tomography and ‐radiography (BAMline) at the Berliner storage ring for synchrotron radiation (BESSY). In computed tomography, the contrast at interfaces within heterogeneous materials can be strongly amplified by effects related to X‐ray refraction. Such effects are especially useful for materials of low absorption or mixed phases showing similar X‐ray absorption properties that produce low contrast. The technique is based on ultra‐small‐angle scattering by microstructural elements causing phase‐related effects, such as refraction and total reflection. The extraordinary contrast of inner surfaces is far beyond absorption effects. Crack orientation and fibre/matrix debonding in plastics, polymers, ceramics and metal‐matrix‐composites after cyclic loading and hydro‐thermal aging can be visualized. In most cases, the investigated inner surface and interface structures correlate to mechanical properties. The technique is an alternative to other attempts on raising the spatial resolution of CT machines.     

Precision Nanocluster-Based Toroidal and Supertoroidal Frameworks Using Photocycloaddition-Assisted Dynamic Covalent Chemistry

Atomically precise nanoclusters (NCs) have recently emerged as ideal building blocks for constructing self-assembled multifunctional superstructures. The existing structures are based on various non-covalent interactions of the ligands on the NC surface, resulting in inter-NC interactions. Despite recent demonstrations on light-induced reversible self-assembly, long-range reversible self-assembly based on dynamic covalent chemistry on the NC surface has yet to be investigated. Here, it is shown that Au₂₅ NCs containing thiolated umbelliferone (7-hydroxycoumarin) ligands allow [2+2] photocycloaddition reaction-induced self-assembly into colloidal-level toroids. The toroids upon further irradiation undergo inter-toroidal reaction resulting in macroscopic supertoroidal honey-comb frameworks. Systematic investigation using electron microscopy, atomic force microscopy (AFM), and electron tomography (ET) suggest that the NCs initially form spherical aggregates. The spherical structures further undergo fusion resulting in toroid formation. Finally, the toroids fuse into macroscopic honeycomb frameworks. As a proof-of-concept, a cross-photocycloaddition reaction between coumarin-tethered NCs and an anticancer drug (5-fluorouracil) is demonstrated as a model photo-controlled drug release system. The model system allows systematic loading and unloading of the drug during the assembly and disassembly under two different wavelengths. The results suggest that the dynamic covalent chemistry on the NC surface offers a facile route for hierarchical multifunctional frameworks and photocontrolled drug release.     

Development and optimization of self-nanoemulsifying drug delivery systems (SNEDDS) for curcumin transdermal delivery: an anti-inflammatory exposure

The purpose of this work is to develop novel lipid-based self-nanoemulsifying drug delivery systems (SNEDDS) as carriers for transdermal delivery of curcumin. SNEDDS containing black seed oil, medium chain mono- and diglycerides and surfactants, were prepared as curcumin delivery vehicles. Their formation spontaneity, morphology, droplet size, and drug loading were evaluated. Gel preparation containing two of the SNEDDS formulations were used in the carrageenan induced paw edema to evaluate the anti-inflammatory effect. Results showed droplet size as low as 71?nm. The highest drug loading was observed with SNEDDS-F6 of ～45?mg/g. In in-vivo investigation, SNEDDS-F6 exhibited significant anti-inflammatory activities in terms of 80% reduction in paw edema when compared with positive control. The prepared SNEDDS with the elevated entrapment efficiency, good transdermal penetration ability could be a suitable candidate for effective transdermal curcumin skin delivery.     

Feasibility of obtaining in situ nanocapsules through modified self-microemulsifying drug delivery systems. A new manufacturing approach for oral route administration

Nanocapsules (NCs) are submicron-sized core shell systems which present important advantages such as improvement of drug efficacy and bioavailability, prevention of drug degradation, and provision of controlled-release delivery. The available methods for NC production require expensive recovery and purification steps which compromised the morphology of NCs. Industrial applications of NCs have been avoided due to the aforementioned issues. In this study, we developed a new method based on a modified self-microemulsifying drug delivery system (SMEDDS) for in situ NCs production within the gastrointestinal tract. This new methodology does not require purification and recovery steps and can preserve the morphology and the functionality of NCs. The in situ formed NCs of Eudragit^® RL PO were compared with nanospheres (NEs) in order to obtain evidence of their core-shell structure. NCs presented a spherical morphology with a size of 126.2?±?13.1?nm, an ibuprofen encapsulation efficiency of 31.3% and a zeta-potential of 37.4?mV. Additionally, NC density and release profile (zero order) showed physical evidence of the feasibility of NCs in situ creation.     

Damage mechanisms in natural (NR) and synthetic rubber (SBR): nucleation,growth and instability of the cavitation*

Elastomeric matrix composites (EMCs) subjected to static and fluctuating loads basically fail due to the nucleation and growth of defects. Also, high hydrostatic pressure can influence the mechanical behaviour of EMCs. The change in behaviour of EMCs due to the nucleation of cavitations under hydrostatic pressure is studied here to understand the mechanics underlying the damage mechanism. Two types of materials for pancake specimens are used in this study; natural rubber (NR) vulcanized and reinforced by carbon black and synthetic rubber (styrene‐butadiene‐rubber, SBR). In situ observations of uniaxial tension and torsion tests are also presented by using X‐ray computed tomography (CT) (medical scanner) and the results are compared with those from scanning electron microscopy (SEM).     

An adaptive dynamic combined energy minimization model for few‐view computed tomography reconstruction

Recently, the potential harm of electromagnetic radiation used in computed tomography (CT) scanning has been paid much attention to. This makes the few‐view CT reconstruction become an important issue in medical imaging. In this article, an adaptive dynamic combined energy minimization model is proposed for few‐view CT reconstruction based on the compress sensing theory. The L2 energy of the image gradient and the total variation (TV) energy are combined, and the working regions of them are separated adaptively with a dynamic threshold. With the proposed model, the TV model's disadvantageous tendency of uniformly penalize the image gradient irrespective of the underlying image structures is overcome. Numerical experiments of the proposed model are performed with various insufficient data problems in fan‐beam CT and suggest that both the reconstruction speed and quality of the results are generally improved. © 2013 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 23, 44–52, 2013.     

Lossless color medical image compression using adaptive block‐based encoding for human computed tomographic images

The advancement in medical imaging systems such as computed tomography (CT), magnetic resonance imaging (MRI), positron emitted tomography (PET), and computed radiography (CR) produces huge amount of volumetric images about various anatomical structure of human body. There exists a need for lossless compression of these images for storage and communication purposes. The major issue in medical image is the sequence of operations to be performed for compression and decompression should not degrade the original quality of the image, it should be compressed loss lessly. In this article, we proposed a lossless method of volumetric medical image compression and decompression using adaptive block‐based encoding technique. The algorithm is tested for different sets of CT color images using Matlab. The Digital Imaging and Communications in Medicine (DICOM) images are compressed using the proposed algorithm and stored as DICOM formatted images. The inverse process of adaptive block‐based algorithm is used to reconstruct the original image information loss lessly from the compressed DICOM files. We present the simulation results for large set of human color CT images to produce a comparative analysis of the proposed methodology with block‐based compression, and JPEG2000 lossless image compression technique. This article finally proves the proposed methodology gives better compression ratio than block‐based coding and computationally better than JPEG 2000 coding. © 2013 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 23, 227–234, 2013     

Super resolution in CT

The general framework of super resolution in computed tomography (CT) system is introduced. Two data acquisition ways before or after the reconstruction respectively are described. Three models including the sinogram model, the in‐plane model and the z‐axis model, are addressed to adapt super resolution to CT system. The improved iterative back projection algorithm is used in this work. Experimental results based on simulated data, GE performance phantom scanned by GE LightSpeed VCT system, one patient volunteer scanned by TOSHIBA Aquilion system, and a special experimental apparatus demonstrate that super resolution is effective to improve the resolution of CT images. The sinogram model is suitable for future CT system; the in‐plane model is restricted to some special clinical diagnoses; and the z‐axis model is practicable for current general clinical CT images. © 2015 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 25, 92–101, 2015     

Image reconstruction with a shift‐variant filtration in circular cone‐beam CT

It is well known that cone‐beam data acquired with a circular orbit are insufficient for exact image reconstruction. Despite this, because a cone‐beam scanning configuration with a circular orbit is easy to implement in practice, it has been widely employed for data acquisition in, e.g., micro‐CT and CT imaging in radiation therapy. The algorithm developed by Feldkamp, Davis, and Kress (FDK) and its modifications, such as the Tent–FDK (T‐FDK) algorithm, have been used for image reconstruction from circular cone‐beam data. In this work, we present an algorithm with spatially shift‐variant filtration for image reconstruction in circular cone‐beam CT. We performed computer‐simulation studies to compare the proposed and existing algorithms. Numerical results in these studies demonstrated that the proposed algorithm has resolution properties comparable to, and noise properties better than, the FDK algorithm. As compared to the T‐FDK algorithm, our proposed algorithm reconstructs images with an improved in‐plane spatial resolution. © 2005 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 14, 213–221, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ima.20026     

Mesoporous titanium dioxide@ zinc oxide–graphene oxide nanocarriers for colon-specific drug delivery

In this project, TiO₂@ZnO nanoparticles core–shell nanostructured and titanium dioxide@ mesoporous zinc oxide–graphene oxide (TiO₂@ZnO–GO) hybrid nanocomposites as controlled targeted drug delivery systems were synthesized by a facile sono-chemical method. We prepared a novel mesoporous and core–shell structure as a drug nanocarrier (NCs) for the loading and pH-responsive characteristics of the chemotherapeutic curcumin. The structure, surface charge, and surface morphology of NCs were studied using with X-ray diffraction, Fourier transform infrared spectroscopy, dynamic light scattering, brunauer–emmett–teller, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The SEM and TEM images of NCs show the uniform hexagonal mesoporous morphology with average grain size of about ～ 190 nm. The drug loading was very high about 16 and 19 for TiO₂@ZnO and TiO₂@ZnO–GO, respectively. The NCs showed pH-dependent drug release behavior. Drug release from TiO₂@ZnO–GO in neutral pH were higher than in acidic medium, due to anionic charge of GO nanosheet. MTT assay results showed that the curcumin-loaded NCs showed significant toxicity due to which cell viability reduced to below 50% at 140 μg/mL concentration, thereby confirming its anticancer effects. The goal of this study is the application of water-dispersed TiO₂@ZnO–GO with pH-dependent release properties for design a new drug delivery carrier.     

Preloading of Hydrophobic Anticancer Drug into Multifunctional Nanocarrier for Multimodal Imaging,NIR‐Responsive Drug Release,and Synergistic Therapy

Applications of hydrophobic drug‐based nanocarriers (NCs) remain largely limited because of their low loading capacity. Here, development of a multifunctional hybrid NC made of a magnetic Fe3O4 core and a mesoporous silica shell embedded with carbon dots (CDs) and paclitaxel (PTX), and covered by another layer of silica is reported. The NC is prepared via a one‐pot process under mild condition. The PTX loading method introduced in this study simplifies drug loading process and demonstrates a high loading capacity due to mesoporous silica dual‐shell structure, supramolecular π‐stacking between conjugated rings of PTX molecules, and aromatic rings of the CDs in the hybrid NC. The CDs serve as both confocal and two‐photon fluorescence imaging probes, while the Fe3O4 core serves as a magnetic resonance imaging contrast agent. Significantly, NC releases PTX in response to near infrared irradiation as a result of local heating of the embedded CDs and the heating of CDs also provides an additional therapeutic effect by thermally killing cancer cells in tumor in addition to the chemotherapeutic effect of released PTX. Both in vitro and in vivo results show that NC demonstrates high therapeutic efficacy through a synergistic effect from the combined chemo‐photothermal treatments.     

Fatigue testing and non‐destructive characterization of AlSi9Cu3(Fe) die cast specimens by computer tomography

AlSi9Cu3(Fe) aluminum alloy fatigue test specimens were produced by high pressure die casting (HPDC) and vacuum‐assisted die casting (VPDC) techniques. Non‐destructive material tests (NDT) have been performed on cast specimens by computed tomography (CT). Uniaxial fatigue tests with two stress ratios of R = ?1 and R = 0.1 have been performed in the high cycle fatigue (HCF) regime, and the CT results were reassigned after the fatigue test in order to identify the origin of the failure. The aim of this paper is to establish a relationship between the CT result and fatigue failure of die cast specimens. The location and the size of the casting defect determine the specimen fatigue life. It has also been found that the fatigue life is determined not only by the size of the defect but also by its location with respect to the position of the highly stressed area. The results can be used to judge the applicability of cast parts after non‐destructive testing.     

Attenuating noise from computed tomography medical images using a coefficients‐driven total variation denoising algorithm

The aim of image denoising is to recover a visually accepted image from its noisy observation with as much detail as possible. The noise exists in computed tomography images due to hardware errors, software faults and/or low radiation dose. Because of noise, the analysis and extraction of accurate medical information is a challenging task for specialists. Therefore, a novel modification on the total variational denoising algorithm is proposed in this article to attenuate the noise from CT images and provide a better visual quality. The newly developed algorithm can properly detect noise from the other image components using four new noise distinguishing coefficients and reduce it using a novel minimization function. Moreover, the proposed algorithm has a fast computation speed, a simple structure, a relatively low computational cost and preserves the small image details while reducing the noise efficiently. Evaluating the performance of the proposed algorithm is achieved through the use of synthetic and real noisy images. Likewise, the synthetic images are appraised by three advanced accuracy methods –Gradient Magnitude Similarity Deviation (GMSD), Structural Similarity (SSIM) and Weighted Signal‐to‐Noise Ratio (WSNR). The empirical results exhibited significant improvement not only in noise reduction but also in preserving the minor image details. Finally, the proposed algorithm provided satisfying results that outperformed all the comparative methods.     

Multifunctional RbxWO3 Nanorods for Simultaneous Combined Chemo‐photothermal Therapy and Photoacoustic/CT Imaging

Light‐triggered drug delivery based on near‐infrared (NIR)‐mediated photothermal nanocarriers has received tremendous attention for the construction of cooperative therapeutic systems in nanomedicine. Herein, a new paradigm of light‐responsive drug carrier that doubles as a photothermal agent is reported based on the NIR light‐absorber, Rb _x WO₃ (rubidium tungsten bronze, Rb‐TB) nanorods. With doxorubicin (DOX) payload, the DOX‐loaded Rb‐TB composite (Rb‐TB‐DOX) simultaneously provides a burst‐like drug release and intense heating effect upon 808‐nm NIR light exposure. MTT assays show the photothermally enhanced antitumor activity of Rb‐TB‐DOX to the MCF‐7 cancer cells. Most remarkably, Rb‐TB‐DOX combined with NIR irradiation also shows dramatically enhanced chemotherapeutic effect to DOX‐resistant MCF‐7 cells compared with free DOX, demonstrating the enhanced efficacy of combinational chemo‐photothermal therapy for potentially overcoming drug resistance in cancer chemotherapy. Furthermore, in vivo study of combined chemo‐photothermal therapy is also conducted and realized on pancreatic (Pance‐1) tumor‐bearing nude mice. Apart from its promise for cancer therapy, the as‐prepared Rb‐TB can also be employed as a new dual‐modal contrast agent for photoacoustic tomography and (PAT) X‐ray computed tomography (CT) imaging because of its high NIR optical absorption capability and strong X‐ray attenuation ability, respectively. The results presented in the current study suggest promise of the multifunctional Rb _x WO₃ nanorods for applications in cancer theranostics.     

A Functional CT Contrast Agent for In Vivo Imaging of Tumor Hypoxia

Hypoxia, which has been well established as a key feature of the tumor microenvironment, significantly influences tumor behavior and treatment response. Therefore, imaging for tumor hypoxia in vivo is warranted. Although some imaging modalities for detecting tumor hypoxia have been developed, such as magnetic resonance imaging, positron emission tomography, and optical imaging, these technologies still have their own specific limitations. As computed tomography (CT) is one of the most useful imaging tools in terms of availability, efficiency, and convenience, the feasibility of using a hypoxia‐sensitive nanoprobe (Au@BSA‐NHA) for CT imaging of tumor hypoxia is investigated, with emphasis on identifying different levels of hypoxia in two xenografts. The nanoprobe is composed of Au nanoparticles and nitroimidazole moiety which can be electively reduced by nitroreductase under hypoxic condition. In vitro, Au@BSA‐NHA attain the higher cellular uptake under hypoxic condition. Attractively, after in vivo administration, Au@BSA‐NHA can not only monitor the tumor hypoxic environment with CT enhancement but also detect the hypoxic status by the degree of enhancement in two xenograft tumors with different hypoxic levels. The results demonstrate that Au@BSA‐NHA may potentially be used as a sensitive CT imaging agent for detecting tumor hypoxia.