Reconstruction of three-dimensional lumbar vertebrae from biplanar x-rays.

Objective. Vertebrae models from computer tomographic (CT) imaging are extensively used in image-guided surgical systems to deliver percutaneous orthopaedic operations with minimum risks, but patients may be exposed to excess radiation from the pre-operative CT scans. Generating vertebrae models from intra-operative x-rays for image-guided systems can reduce radiation exposure to the patient, and the surgeons can acquire the vertebrae's relative positions during the operation; therefore, we proposed a lumbar vertebrae reconstruction method from biplanar x-rays.Approach. Non-stereo-corresponding vertebral landmarks on x-rays were identified as targets for deforming a set of template vertebrae; the deformation was formulated as a minimisation problem, and was solved using the augmented Lagrangian method. Mean surface errors between the models reconstructed using the proposed method and CT scans were measured to evaluate the reconstruction accuracy.Main results. The evaluation yielded mean errors of 1.27 mm and 1.50 mm inin vitroexperiments on normal vertebrae and pathological vertebrae, respectively; the outcomes were comparable to other template-based methods.Significance. The proposed method is a viable alternative to provide digital lumbar to be used in image-guided systems, where the models can be used as a visual reference in surgical planning and image-guided applications in operations where the reconstruction error is within the allowable surgical error.

Construction of a Label-Free Electrochemical Immunosensor Based on Zn-Co-S/Graphene Nanocomposites for Carbohydrate Antigen 19-9 Detection.

Nanocomposites of the binary transition metal sulfide Zn-Co-S/graphene (Zn-Co-S@G) were synthesized through a one-step hydrothermal method. They may be useful in the construction of an electrochemical immunosensor for carbohydrate antigen 19-9 (CA19-9) detection. Zn-Co-S dot-like nanoparticles uniformly covered the surface of graphene to form an interconnected conductive network, ensuring strong interaction between transition metal sulfide and graphene, which can expose numerous electroactive sites leading to the improvement of the amplified electrochemical signal toward a direct reduction of H2O2. Thus, the construction of an electrochemical immunosensor using Zn-Co-S@G nanocomposites showed outstanding sensing properties for detecting CA19-9. The constructed electrochemical immunosensor exhibited a good linear relationship in the range of 6.3 U·mL-1-300 U·mL-1, with the limit of detection at 0.82 U·mL-1, which makes it a promising candidate for an electrochemical immunosensor.

Non-Enzymatic Glucose Sensing Based on Incorporation of Carbon Nanotube into Zn-Co-S Ball-in-Ball Hollow Sphere.

Zn-Co-S ball-in-ball hollow sphere (BHS) was successfully prepared by solvothermal sulfurization method. An efficient strategy to synthesize Zn-Co-S BHS consisted of multilevel structures by controlling the ionic exchange reaction was applied to obtain great performance electrode material. Carbon nanotubes (CNTs) as a conductive agent were uniformly introduced with Zn-Co-S BHS to form Zn-Co-S BHS/CNTs and expedited the considerable electrocatalytic behavior toward glucose electro-oxidation in alkaline medium. In this study, characterization with scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD) was used for investigating the morphological and physical/chemical properties and further evaluating the feasibility of Zn-Co-S BHS/CNTs in non-enzymatic glucose sensing. Electrochemical methods (cyclic voltammetry (CV) and chronoamperometry (CA)) were performed to investigate the glucose sensing performance of Zn-Co-S BHS/CNTs. The synergistic effect of Faradaic redox couple species of Zn-Co-S BHS and unique conductive network of CNTs exhibited excellent electrochemical catalytic ability towards the glucose electro-oxidation, which revealed linear range from 5 to 100 µM with high sensitivity of 2734.4 µA mM-1 cm-2, excellent detection limit of 2.98 µM, and great selectivity in the presence of dopamine, uric acid, ascorbic acid, and fructose. Thus, Zn-Co-S BHS/CNTs would be expected to be a promising material for non-enzymatic glucose sensing.

Multistage Continuous Targeting with Quantitatively Controlled Peptides on Chitosan-Lipid Nanoparticles with Multicore-Shell Nanoarchitecture for Enhanced Orally Administrated Anticancer In Vitro and In Vivo.

A DOX-loaded polysaccharide-lecithin reverse micelles triglyceride-based oral delivery nanocarrier (D-PL/TG NPs) conjugated with (i) RGD peptide for targeting to ß1 integrin of M cells and (ii) Lyp-1 peptide for targeting to the p32 receptor of MDA-MB-231 cells is used to investigate the multistage continuous targeting capabilities of these peptide-conjugated nanocarriers (GLD-PL/TG NPs) for tumor therapy. Variations in the targeting efficacy and pharmacokinetic properties are investigated by quantitatively controlling the surface density of different peptides on the nanoparticles. In vitro permeability in a human follicle-associated epithelium model and cytotoxicity against MDA-MB-231 cells indicate that the nanocarriers conjugated with high RGD peptide concentrations display a higher permeability due to the existence of M cells with higher transcytosis activity, but a higher concentration of conjugated Lyp-1 peptide exhibits the lowest cell viability. Being benefited from specific targeting of peptide conjugation, improved bioavailability and enhanced tumor accumulation are achieved by the GLD-PL/TG NPs, leading to better antitumor efficacy. The results of in vivo biodistribution and antitumor studies reveal that the effect of LyP-1 peptide is more predominant than that of RGD peptide. This proof of multistage continuous targeting may open the door to a new generation of oral drug delivery systems in targeted cancer therapy.

Sodium Dodecyl Sulfate-Modified Doxorubicin-Loaded Chitosan-Lipid Nanocarrier with Multi Polysaccharide-Lecithin Nanoarchitecture for Augmented Bioavailability and Stability of Oral Administration In Vitro and In Vivo.

For oral anti-cancer drug delivery, a new chitosan-lipid nanoparticle with sodium dodecyl sulfate modification was designed and synthesized using a double emulsification. TEM examination showed that the DOX-loaded nanoparticles, termed D-PL/TG NPs, exhibited a unique core-shell configuration composed of multiple amphiphilic chitosan-lecithin reverse micelles as the core and a triglyceride shell as a physical barrier to improve the encapsulation efficiency and reduce the drug leakage. In addition, the D-PL/TG NPs with sodium dodecyl sulfate modification on the surface have enhanced stability in the GI tract and increased oral bioavailability of doxorubicin. In vitro transport studies performed on Caco-2 monolayers indicated that the D-PL/TG NPs enhanced the permeability of DOX in the Caco-2 monolayers by altering the transport pathway from passive diffusion to transcytosis. The in vivo intestinal absorption assay suggested that the D-PL/TG NPs were preferentially absorbed through the specialized membranous epithelial cells (M cells) of the Peyer's patches, resulting in a significant improvement (8-fold) in oral bioavailability compared to that of free DOX. The experimental outcomes in this work demonstrate that the D-PL/TG NPs provide an exciting opportunity for advances in the oral administration of drugs with poor bioavailability that are usually used in treating tough and chronic diseases.

Amifostine-conjugated pH-sensitive calcium phosphate-covered magnetic-amphiphilic gelatin nanoparticles for controlled intracellular dual drug release for dual-targeting in HER-2-overexpressing breast cancer.

We developed a surfactant-free method utilizing amifostine to stably link a targeting ligand (Herceptin) to amphiphilic gelatin (AG)-iron oxide@calcium phosphate (CaP) nanoparticles with hydrophobic curcumin (CUR) and hydrophilic doxorubicin (DOX) encapsulated in the AG core and CaP shell (AGIO@CaP-CD), respectively. This multi-functional nanoparticle system has a pH-sensitive CaP shell and degradable amphiphilic gelatin (AG) core, which enables controllable sequential release of the two drugs. The dual-targeting system of AGIO@CaP-CD (HER-AGIO@CaP-CD) with a bioligand and magnetic targeting resulted in significantly elevated cellular uptake in HER2-overexpressing SKBr3 cells and more efficacious therapy than delivery of targeting ligand alone due to the synergistic cell multi-drug resistance/apoptosis-inducing effect of the CUR and DOX combination. This nanoparticle combined with Herceptin and iron oxide nanoparticles not only provided a dual-targeting functionality, but also encapsulated CUR and DOX as a dual-drug delivery system for the combination therapy. This study further demonstrated that the therapeutic efficacy of this dual-targeting co-delivery system can be improved by modifying the application duration of magnetic targeting, which makes this combination therapy system a powerful new tool for in vitro/in vivo cancer therapy, especially for HER2-positive cancers.

In situ DOX-calcium phosphate mineralized CPT-amphiphilic gelatin nanoparticle for intracellular controlled sequential release of multiple drugs.

A co-delivery strategy has been developed to achieve the synergistic effect of a hydrophobic drug (camptothecin, CPT) and a hydrophilic drug (doxorubicin, DOX) by utilizing the unique structure of amphiphilic gelatin/camptothecin @calcium phosphate-doxorubicin (AG/CPT@CaP-DOX) nanoparticles as a carriers in order to replace double emulsions while preserving the advantages of inorganic materials. The hydrophobic agent (CPT) was encapsulated via emulsion with an amphiphilic gelatin core, and subsequently mineralized by CaP-hydrophilic drug (DOX) through precipitation to form a CaP shell on the CPT-AG amphiphilic gelatin core so that drug molecules with different characteristics (i.e. hydrophobic and hydrophilic) can be encapsulated in different regions to avoid their interaction. The existence of the CaP shell can protect the DOX against free release and cause an increased transfer of DOX across membranes, overcoming multidrug resistance. Release studies from core-shell carriers showed the possibility of achieving sequential release of more than one type of drug by controlling the pH-sensitive CaP shell and degradable AG core. The highly pH-responsive behavior of the carrier can modulate the dual-drug-release of DOX/CPT, specifically in acidic intracellular pH environments. The AG/CPT@CaP-DOX nanoparticles also exhibited higher drug efficiencies against MCF-7/ADR cells than MCF-7 cells, thanks to a synergistic cell cycle arrest/apoptosis-inducing effect between CPT and DOX. As such, this core-shell system can serve as a general platform for the localized, controlled, sequential delivery of multiple drugs to treat several diseases, especially for multidrug-resistant cancer cells.

Multifunctional nanocarriers for simultaneous encapsulation of hydrophobic and hydrophilic drugs in cancer treatment.

Combination therapy for cancer patients is an important standard of care protocol because it can elicit synergistic therapeutic effects and reduce systemic toxicity by simultaneously modulating multiple cell-signaling pathways and overcoming multidrug resistance. Nanocarriers are expected to play a major role in delivering multiple drugs to tumor tissues by overcoming biological barriers. However, especially considering the different physical chemistry of chemotherapeutic drugs, it is highly desirable to develop a codelivery nanocarrier for controlled and targeted delivery of both hydrophobic and hydrophilic drugs. This review reports the recent developments in various combinational drug delivery systems and the simultaneous use of combinational drug delivery systems with functional agents.

Synergistic combination therapy using a lipid shell-droplet core nanosphere with tunable thickness.

A newly-designed drug carrier composed of an internal droplet core and a thickness-controllable shell was successfully developed. By co-delivering paclitaxel, doxorubicin and quantum dots simultaneously, this combinational drug delivery system could achieve in vitro fluorescence imaging, chemotherapeutic and oxidation therapy.

Polysaccharide-lecithin reverse micelles with enzyme-degradable triglyceride shell for overcoming tumor multidrug resistance.

A newly-designed drug carrier with enzyme-triggered release behavior and the ability to circumvent multidrug resistance was successfully developed. By optimizing the ratio of lecithin and polysaccharide in reverse micelles, encapsulation efficiency and encapsulation stability can be significantly improved.

A Nanodot Array Modulates Cell Adhesion and Induces an Apoptosis-Like Abnormality in NIH-3T3 Cells.

Micro-structures that mimic the extracellular substratum promote cell growth and differentiation, while the cellular reaction to a nanostructure is poorly defined. To evaluate the cellular response to a nanoscaled surface, NIH 3T3 cells were grown on nanodot arrays with dot diameters ranging from 10 to 200 nm. The nanodot arrays were fabricated by AAO processing on TaN-coated wafers. A thin layer of platinum, 5 nm in thickness, was sputtered onto the structure to improve biocompatibility. The cells grew normally on the 10-nm array and on flat surfaces. However, 50-nm, 100-nm, and 200-nm nanodot arrays induced apoptosis-like events. Abnormality was triggered after as few as 24 h of incubation on a 200-nm dot array. For cells grown on the 50-nm array, the abnormality started after 72 h of incubation. The number of filopodia extended from the cell bodies was lower for the abnormal cells. Immunostaining using antibodies against vinculin and actin filament was performed. Both the number of focal adhesions and the amount of cytoskeleton were decreased in cells grown on the 100-nm and 200-nm arrays. Pre-coatings of fibronectin (FN) or type I collagen promoted cellular anchorage and prevented the nanotopography-induced programed cell death. In summary, nanotopography, in the form of nanodot arrays, induced an apoptosis-like abnormality for cultured NIH 3T3 cells. The occurrence of the abnormality was mediated by the formation of focal adhesions.

Picogram detection of metal ions by melanin-sensitized piezoelectric sensor.

A heavy metal ion sensor was constructed by cross-linking melanin onto the gold electrode of quartz crystal microbalance (QCM). A mercury ion sensitivity of 518+/-37 Hz/ppm was observed, a substantial increase in sensitivity compared to previous reports of 10-50 Hz/ppm with the limit of detection at 5 ppb. Detection of other metal ions including Sn(2+), Ge(4+), Li(+), Zn(2+), Cu(2+), Bi(3+), Co(2+), Al(3+), Ni(2+), Ag(+), and Fe(3+) were also performed. Unexpectedly, binding of Mn(7+), Pb(2+), Cd(2+), and Cr(3+) increased resonant frequencies. The surface profile of melanin thin film upon binding to metal ions was investigated by atomic force microscopy (AFM). Structural change of melanin upon binding to metal ions was characterized by circular dichroism and by infrared spectroscopy. The current study provides the first example of melanin-coated piezoelectric sensor showing high sensitivity and selectivity to metal ions.