Fabrication of a Multimodal Microbubble Platform for Magnetic Resonance, Ultrasound and Fluorescence Imaging Application.

Magnetic resonance (MR), ultrasound (US) and fluorescence imaging are the widely used diagnostic modalities for various experimental and clinical applications. A multimodal poly(lactic acid) microbubble (MB) integrated with the three imaging modalities was fabricated by adsorbing CdTe quantum dots (QDs) onto the surface and encapsulating superparamagnetic iron oxide (SPIO) nanoparticles into the core. The strong fluorescence of the multimodal MBs confirmed that QDs were successfully deposited onto the surface. The in vitro MRI contrasting capability of the multimodal MBs at various concentrations was evaluated by T2-weighted imaging. Furthermore, the in vitro and in vivo ultrasonography indicated that CdTe and SPIO-inclusive MBs maintained excellent ultrasound contrast property. These results implied that the nano-in-micro hybrid materials have the potential as a nanomedical platform for multimodal bioimaging.

Multifunctional ultrasound contrast agents for imaging guided photothermal therapy.

Among all the imaging techniques, ultrasound imaging has a unique advantage due to its features of real-time, low cost, high safety, and portability. Ultrasound contrast agents (UCAs) have been widely used to enhance ultrasonic signals. One of the most exciting features of UCAs for use in biomedicine is the possibility of easily putting new combinations of functional molecules into microbubbles (MBs), which are the most routinely used UCAs. Various therapeutic agents and medical nanoparticles (quantum dots, gold, Fe3O4, etc.) can be loaded into ultrasound-responsive MBs. Hence, UCAs can be developed as multifunctional agents that integrate capabilities for early detection and diagnosis and for imaging guided therapy of various diseases. The current review will focus on such state-of-the-art UCA platforms that have been exploited for multimodal imaging and for imaging guided photothermal therapy.

Determination of trace copper ions with ultrahigh sensitivity and selectivity utilizing CdTe quantum dots coupled with enzyme inhibition.

A fluorescent transducer with the combination of the unique property of CdTe quantum dots (QDs) and enzymatic inhibition assays was successfully constructed for the purpose of ultrasensitive determination of Cu(2+) ions. Alcohol oxidase (AO) catalyzed the oxidation of methanol to produce hydrogen peroxide (H(2)O(2)), inducing the quenching of QDs fluorescence. In the presence of Cu(2+) ions, the activity of AO was inhibited and therefore, the quenching of QDs fluorescence was decreased. Other metal ions showed no intensive inhibition to the AO activity even at 10 or 100 times Cu(2+) ions concentration, presenting a high selectivity of this fluorescent sensor. Using this QDs-enzyme hybrid system, the detection limit for Cu(2+) ions was found to be as low as 0.176 ng/mL (2.75 nM) due to the superior fluorescence property of QDs. Practical application of the QDs-enzyme hybrid system has been demonstrated by domestic waste water, agricultural irrigation water and lake water analysis. Results of Cu(2+) determinations were in good agreement with those obtained by inductively coupled plasma analytical method. The coupling of efficient quenching of QDs photoluminescence by H(2)O(2) generated from oxidase-catalyzed reaction and the effective enzymatic inhibition make this a simple and sensitive method for heavy metal ions detection.

In vitro evaluation and finite element simulation of drug release from polydiacetylene-polyethylene glycol stearate nanovesicles.

Vesicles comprised of 10,12-pentacosadiynoic acid (PCDA) were modified, using polyethylene glycol 40 stearate (PEG40S), and crosslinked by ultraviolet (UV) irradiation to create polymerized nanovesicles for sustained drug release. Paclitaxel, a water-insoluble compound widely used in cancer chemotherapy, was used as a model drug to examine the physicochemical stability and release profiles of PCDA/PEG40S nanovesicles. TEM analysis revealed the formation of paclitaxel-encapsulated PCDA/PEG40S nanovesicles of 40 to 200 nm in size. Upon the addition of ethanol, instantaneous releases of paclitaxel in the amount of 28 microg/mL from polymerized PCDA/PEG40S nanovesicles and 108 microg/ml from unpolymerized ones were observed. This suggested the non-complete drug release from polymerized PCDA/PEG40S nanovesicles due to their enhanced physicochemical stability by ultraviolet irradiation-induced polymerization, if compared to unpolymerized ones. An in vitro study demonstrated that an accumulative release of 24.1 +/- 3.1% and 8.1 +/- 1.7% of paclitaxel was obtained within 24 hrs from nanovesicles comprised of PCDA/PEG40S at a 9:1 and 7:3 molar ratio, respectively. A finite element model that considered the diffusion-driven releases and the reversible drug-vesicle interaction captured the sustained release of paclitaxel from polymerized PCDA/PEG40S nanovesicles. PCDA/PEG40S nanovesicles capable of sustained release and with enhanced physicochemical stability thus possess great potential for applications in drug release.

Free-standing liposomal nanohybrid cerasomes as ideal materials for sensing of cupric ions.

Super-stable and free-standing cerasomes with inorganic polyorganosiloxane surfaces were developed for the sensing of Cu(2+) by encapsulating Nile red (NR) dye as a fluorescence reporter. 1,2-Dimynistoyl-sn-glycero-3-phosphatidylethanolamine (DMPE) was incorporated into the cerasomes to serve as the chelating agent for cupric ions. The intraparticle energy transfer from NR to Cu(2+) caused the fluorescence quenching of NR, showing the prospect of these cerasomes as a fluorescence "turn-off" sensor for the detection of trace copper ions.

Polydiacetylene vesicles as a novel drug sustained-release system.

Aiming at the enhancement of the physicochemical stability as well as the sustained-release property of conventional liposomes, a novel polymerized vesicular carrier, 10,12-pentacosadiynoic acid (PCDA) vesicles, loaded with paclitaxel as a model hydrophobic drug has been successfully constituted by incorporation of a polymerizable diacetylene into the lipid bilayer vesicles. The polymerized vesicles have been characterized in terms of particle size distribution and zeta-potential. Altering their lipid composition causes the zeta-potential to change from -3+/-1mV to more than -25mV, with a concomitant change in particle size distribution from 29+/-4nm to 149+/-18nm. Dynamic light scattering (DLS) showed that the stability of polymerized vesicles against Triton X-100 was improved greatly compared with the conventional liposomes. In vitro drug release studies show that PCDA-incorporating vesicles reduce the paclitaxel release over the conventional phospholipids vesicles. 69+/-6% paclitaxel is released within 24h from the conventional vesicles, but the insertion of 50% and 75% molar ratio of PCDA changes the amount to 57+/-1% and 32+/-4%, respectively. Our results demonstrate that such novel polymerized vesicles have very good prospect as an anticancer drug carrier.

A promising drug controlled-release system based on diacetylene/phospholipid polymerized vesicles.

A novel polymerized vesicular carrier loaded with paclitaxel was developed by introducing the ultraviolet (UV) cross-linkable 10,12-pentacosadiynoic acid (PCDA) into bilayered phospholipid vesicles with the purpose of improving the physicochemical stability as well as the controlled-release property of liposomes. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) results revealed the enhanced stability of PCDA-polymerized vesicles against Triton X-100. In particular, alteration in PCDA/phospholipids ratios and UV-irradiation time can modulate the cumulative paclitaxel released. For instance, vesicles composed of phospholipids only released 98.0 +/- 2.1% of paclitaxel within 24 h. Over the same time period, 72.0 +/- 5.8%, 43.9 +/- 6.5%, and 20.1 +/- 5.4% of paclitaxel was released from polymerized PCDA/phospholipid vesicles at molar ratios of 1:3, 1:1, and 3:1, respectively. Likewise, by increasing the UV-irradiation time from 20 to 40 min, the cumulative release of paclitaxel from polymerized PCDA/phospholipid vesicles at molar ratio of 1:1 decreased from 90.5 +/- 3.7% to 37.6 +/- 2.3% over a time period of experimental observation of 24 h. The influences of vesicle composition (i.e., PCDA/phospholipids ratio) and UV-irradiation time on the release rates of paclitaxel were further examined by finite element (FE) analyzed using Abaqus. Our results demonstrate that novel polymerized vesicles capable of regulating the release of anticancer drugs such as paclitaxel have been developed.

Quantum-dot-modified microbubbles with bi-mode imaging capabilities.

The aim of this paper was to develop a novel bi-mode ultrasound/fluorescent imaging agent through stepwise layer-by-layer deposition of poly(allylamine hydrochloride) (PAH) and CdTe quantum dots (QDs) onto ST68 microbubbles (MBs) produced by sonication of a mixture of surfactants (Span 60 and Tween 80). The experiments using photoluminescence spectroscopy and confocal laser scanning microscopy confirmed that CdTe nanoparticles were successfully adsorbed on the outer surface of the MBs. The static light scattering measurements showed that size distributions of MBs before and after QD deposition met the size requirements for clinical application. The in vitro and in vivo ultrasonography indicated that the QD-modified MBs maintained good contrast enhancement properties as the original MBs. Furthermore, the in vitro ultrasound-targeted microbubble destruction (UTMD) experiment of the QD-MB composites was carried out to validate the ability of MBs to deliver QDs for fluorescent imaging. The results showed that the QD-modified MBs not only maintained the capability of ultrasound imaging, but also could be used as a targeted-drug controlled-release system to deliver the QDs for cell and tissue fluorescent imaging by UTMD. The novel dual-functional imaging agent has potential for a variety of biological and medical applications.

One-step immobilization of alkanethiol/glycolipid vesicles onto gold electrode: amperometric detection of Concanavalin A.

Functionalized vesicles composed of glycolipid and alkanethiol lipids have been immobilized onto gold surface through one-step self-assembly to construct an electrochemical biosensor for Concanavalin A (Con A) detection. Incorporation of alkanethiol lipid molecules into the vesicles allows for firm attachment of the vesicles onto a gold surface to form a sensing interface. At the same time, the introduction of alkanethiol lipid avoids cumbersome organic syntheses of sulfur-containing compound, making the biosensor greater applied prospect. Through the recognition of Con A by glycolipid which was immobilized on the surface of electrode, a decrease of electrochemical signal was observed. This decrease was restored when the electrode was immersed in a stronger binding solution such as glucose. The repeated usability of the novel sensor is excellent.

Investigation on the temperature effect of a mixed vesicle composed of polydiacetylene and BODIPY 558.

BODIPY 558 is an insensitive fluorescent reagent to temperature. But when it is inserted into polydiacetylene (PDA) vesicles, the resultant complex presents a considerable temperature effect. In this article, we reported the temperature-dependent fluorescence intensity of a vesicle-based sensor constructed by PDA and BODIPY fluorescent probe. The fluorescence of BODIPY was considerably quenched in the polymerized diacetylene lipid membrane, but recovered by increasing the temperature of vesicle solution. The mechanism of quenching was detailedly investigated, and we deduced that the fluorescence quenching and recovery were associated with the conjugated conformation of the PDA backbone.

Highly sensitive gold nanoparticles biosensor chips modified with a self-assembled bilayer for detection of Con A.

In this paper, an improved method for detection of Concanavalin A (Con A) with label-free optical biosensors is reported. 1-Dodecanethiol (DDT) was self-assembled onto gold nanoparticles which were deposited on glass slides, and then glycolipid molecules were inserted into dodecanethiol by physical interactions only. The recognition between Con A and carbohydrate was observed by UV-vis spectrophotometry. The absorption spectrum shifted when Con A was bound to the sugar residues of glycolipids immobilized onto nanogold slides, while almost no spectrum change was observed when another nonspecific protein molecule met the nanogold slides. The self-assembled bilayer on nanogold substrates had very high sensitivity for Con A, the minimum detection concentration of Con A can be down to 0.1 nM. In addition to the ultra sensitivity for investigating carbohydrate-lectin interaction, the self-assembled bilayer structure, is expected to replace many receptors which require time-consuming organic syntheses for the fixation to the transducer. The simplicity and sensitivity of this biosensor architecture once again show the prospect of nanogold application in biosensor.

Synthesis and characterization of Dy(OH)3 and Dy2O3 nanotubes.

Dy(OH)3 nanotubes with high aspect ratios of up to about 50 were synthesized in the presence of poly(ethylene glycol) via a hydrothermal method. Poly(ethylene glycol), as a nonionic surfactant, plays an important role in the formation of morphologies. Subsequent thermal treatment of Dy(OH)3 nanotube precursors at 450 degrees C for 6 h led to Dy2O3 nanotubes, during which the precursor tubular morphology was maintained. Selected-area electron diffraction and high-resolution transmission electron microscopy reveal the single-crystal nature of the Dy(OH)3 and Dy2O3 nanotubes. The morphologies and crystalline structure of the as-obtained products were characterized by scanning electron microscopy, transmission electron microscopy, and X-ray diffraction, respectively. By this method, we can obtain a mass of products.

Controlled synthesis of LaPO(4) and CePO(4) nanorods/nanowires.

LaPO(4) and CePO(4) nanorods/nanowires with controlled aspect ratios have been successfully synthesized using a hydrothermal microemulsion method under mild conditions. It has been shown that the obtained LaPO(4) has a monoclinic structure, while CePO(4) exists in the hexagonal structure. Uniform nanorods/nanowires with diameters of 20-60 nm and lengths ranging from several hundreds of nanometres to several micrometres were obtained. The aspect ratios of the obtained 1D nanostructures can be fine-tuned by simply changing the [H(2)O ]/[surfactant] molar ratios. The possible growth mechanism of LaPO(4) and CePO(4) nanorods/nanowires was explored in detail.

A simple route towards CuO nanowires and nanorods.

CuO nanowires and nanorods were synthesized through a novel controllable solution-phase hydrothermal method using a nonionic surfactant polyethylene glycol (PEG) as the structure-directing template. The lengths of obtained 1D CuO nanostructures could be successfully controlled through choosing different molecular weights of PEG. The phase structures and morphologies were investigated by XRD, TEM, HRTEM and SAED. The formation mechanisms of the nanorods and nanowires were investigated and discussed on the basis of the experimental results.

Shape and size control of ZnO nanostructures via a simple solution route.

ZnO nanostructures with different morphologies were synthesized by condensing the Zn(OH)4(2-) precursors under hydrothermal conditions in the presence of a surfactant, cetyltrimethylammonium bromide (CTAB). Shape and size control of ZnO nanostructures was achieved by relatively simple variations of molar ratio of CTAB to Zn(OH)4(2-). With a higher molar ratio, ZnO nanotubes were obtained, whereas with a lower molar ratio, ZnO nanorods were formed; furthermore, with a moderate w value, the coexistence of ZnO nanorods and nanotubes was also observed. The photoluminescence of ZnO nanorods and nanotubes was also investigated.

A controllable synthetic route to Cu, Cu2O, and CuO nanotubes and nanorods.

Reducing Cu(OH)4(2-) with hydrazine hydrate and glucose in the presence of a structure-directing surfactant at room temperature gave Cu and Cu2O nanotubes/nanorods, respectively, whereas facile hydrothermal treatment of Cu(OH)4(2-) precursor resulted in CuO nanotubes/nanorods.

Self-assembled multilayer films based on a Keggin-type polyoxometalate and polyaniline.

Multilayer ultrathin films were fabricated from partially doped polyaniline (PAN) and a Keggin-type polyoxometalate [alpha-SiW(12)O(40)](4-) (alpha-SiW(12)) in aqueous solution via the layer-by-layer self-assembly technique and characterized by UV-vis, FTIR, and X-ray photoelectron spectra (XPS), ellipsometry, scanning electron microscopy (SEM), and atomic force microscopy (AFM). UV-vis spectroscopy shows that the absorbance values at characteristic wavelengths of the multilayer films increase almost linearly with the number of PAN/alpha-SiW(12) bilayers, suggesting that the deposition process is regular and highly reproducible from layer to layer. FTIR and XPS spectra confirm the incorporation of alpha-SiW(12) and PAN into the films. Ellipsometric measurements show that the PAN/alpha-SiW(12) bilayer thickness increases with the increasing PAN solution concentration. SEM and AFM images indicate that the film surface is relatively uniform and smooth. In addition, the electrical conductivities of the multilayer films doped with hydrochloric acid were also measured.