Broaden sources and reduce expenditure: Tumor-specific transformable oxidative stress nanoamplifier enabling economized photodynamic therapy for reinforced oxidation therapy.

Cancer cells immersed in inherent oxidative stress are more vulnerable to exogenous oxidative damages than normal cells. Reactive oxygen species (ROS)-mediated oxidation therapy preferentially aggravating tumor oxidative stress to disrupt redox homeostasis, has emerged as an effective and specific anticancer treatment. Herein, following an ingenious strategy of "broaden sources and reduce expenditure", we designed a versatile tumor-specific oxidative stress nanoamplifier enabling economized photodynamic therapy (PDT), to achieve synergistic oxidative stress explosion for superior oxidation therapy. Methods: Cinnamaldehyde (CA) as a therapeutic ROS generator was first conjugated to hyaluronic acid (HA) through acid-labile hydrazone bond to synthesize tailored amphiphilic HA@CA conjugates, which could surprisingly self-assemble into uniform nanofibers in aqueous media. Photosensitizer protoporphyrin (PpIX) was efficiently encapsulated into HA@CA nanofibers and transformed HA@CA nanofibers to final spherical HA@CAP. Results: With beneficial pH-responsiveness and morphology transformation, improved bioavailability and selective tumor accumulation, HA@CAP combining ROS-based dual chemo/photodynamic treatment modalities could induce cytotoxic ROS generation in a two-pronged approach to amplify tumor oxidative stress, termed "broaden sources". Moreover, utilizing CA-induced H2O2 production and cascaded Fenton reaction in mitochondria to consume intracellular overloaded Fe(II), HA@CAP could skillfully block endogenic heme biosynthesis pathway on site to restrain undesired elimination of PpIX for economized PDT, termed "reduce expenditure". Both in vitro and in vivo results demonstrated the superior antitumor performance of HA@CAP. Conclusion: This study offered an inspiring strategy of "broaden sources and reduce expenditure" to specifically boost tumor oxidative stress for reinforced oxidation therapy.

An anti-inflammatory nanoagent for tumor-targeted photothermal therapy.

We developed an anti-inflammatory nanoagent by combining polydopamine nanospheres with aspirin and cancer cell membrane coating, which can effectively kill cancer cells and simultaneously eliminate photothermal therapy-induced inflammation.

A dual-mode nanoprobe for evaluation of the autophagy level affected by photothermal therapy.

A novel dual-mode nanoprobe (Apt@MNPS) was created for the detection of autophagy-related miRNAs to monitor the autophagic level and study the effect of PTT on autophagy. Interestingly, using our developed probe, PTT was found to be able to activate the autophagy by down regulation of miR-18a* and miR-4802, which in turn restricted the PTT efficiency for cancer.

Endo- and Exo-Functionalized Tetraphenylethylene M12L24 Nanospheres: Fluorescence Emission inside a Confined Space.

The intrinsic relationship between the properties of green fluorescent protein (GFP) and its encapsulated small molecular light machine has spurred many biomimicking studies, aiming at revealing the detailed mechanism and further promoting its wide applications in different disciplines. However, how to build a similar confined microenvironment to mimic the cavity of a ß-barrel and the fluorescence turn-on process is a fundamental challenge for both chemists and biologists. Herein, two distinct exo- and endo-functionalized tetraphenylethylene (TPE)-based M12L24 nanospheres with precise distribution of anchored TPE moieties and unique photophysical properties were constructed by means of a coordination-driven self-assembly strategy. Under dilute conditions, the nanospheres fluoresce more strongly than the corresponding TPE subcomponents. Meanwhile, the endo-functionalized sphere is able to induce a higher local concentration and more restrained motion of the enclosed 24 TPE units compared with exo-functionalized counterpart and thus induces much stronger emission due to the restriction of the rotation of the pendant TPE units. The biomimetic methodology developed here represents a promising way to understand and construct artificial GFP materials on the platforms of supramolecular coordination complexes.

Noninvasive, targeted gene therapy for acute spinal cord injury using LIFU-mediated BDNF-loaded cationic nanobubble destruction.

Various gene delivery systems have been widely studied for the acute spinal cord injury (SCI) treatment. In the present study, a novel type of brain-derived neurotrophic factor (BDNF)-loaded cationic nanobubbles (CNBs) conjugated with MAP-2 antibody (mAbMAP-2/BDNF/CNBs) was prepared to provide low-intensity focused ultrasound (LIFU)-targeted gene therapy. In vitro experiments, the ultrasound-targeted tranfection to BDNF overexpressioin in neurons and efficiently inhibition neuronal apoptosis have been demonstrated, and the elaborately designed mAbMAP-2/BDNF/CNBs can specifically target to the neurons. Furthermore, in a acute SCI rat model, LIFU-mediated mAbMAP-2/BDNF/CNBs transfection significantly increased BDNF expression, attenuated histological injury, decreased neurons loss, inhibited neuronal apoptosis in injured spinal cords, and increased BBB scores in SCI rats. LIFU-mediated mAbMAP-2/BDNF/CNBs destruction significantly increase transfection efficiency of BDNF gene both in vitro and in vivo, and has a significant neuroprotective effect on the injured spinal cord. Therefore, the combination of LIFU irradiation and gene therapy through mAbMAP-2/BDNF/CNBs can be considered as a novel non-invasive and targeted treatment for gene therapy of SCI.

Highly Hydrophilic Luminescent Magnetic Mesoporous Carbon Nanospheres for Controlled Release of Anticancer Drug and Multimodal Imaging.

Judicious combination of fluorescence and magnetic properties along with ample drug loading capacity and control release property remains a key challenge in the design of nanotheranostic agents. This paper reports the synthesis of highly hydrophilic optically traceable mesoporous carbon nanospheres which can sustain payloads of the anticancer drug doxorubicin and T2 contrast agent such as cobalt ferrite nanoparticles. The luminescent magnetic hybrid system has been prepared on a mesoporous silica template using a resorcinol-formaldehyde precursor. The mesoporous matrix shows controlled release of the aromatic drug doxorubicin due to disruption of supramolecular π-π interaction at acidic pH. The particles show MR contrast behavior by affecting the proton relaxation with transverse relaxivity (r2) 380 mM(-1) S(-1). The multicolored emission and upconversion luminescence property of our sample are advantageous in bioimaging. In vitro cell experiments shows that the hybrid nanoparticles are endocyted by the tumor cells through passive targeting. The pH-responsive release of doxorubicin presents chemotherapeutic inhibition of cell growth through induction of apoptosis.

Facile Preparation of Bifunctional Monodisperse Nanospheres with Tunable Size and Luminescence.

Nanotechnology has found wide use in biomedical applications and the food and bioprocessing industry. In this light, we demonstrate a facile strategy to prepare bifunctional monodisperse silica nanospheres encapsulating chitosan-coated magnetic nanoparticles and CdTe quantum dots. The size of these composite spheres can be adjusted from 90 nm to 500 nm by varying the concentration of ammonia, water, tetraethyl orthosilicate, and the ratio of the chitosan-coated magnetic nanoparticles and CdTe quantum dots. The composite spheres are characterized using scanning electron microscope analyses, transmission electron microscope analyses, energy-dispersed spectrum studies, Malvern Zetasizer, vibrating sample magnetometer, and fluorescence microscopy. The spheres exhibit good monodispersion and favorable superparamagnetic and fluorescent properties. The luminescence of the spheres can be varied by using different types of coated quantum dots. Such composite spheres with tunable characteristics allow for external manipulation of research systems by magnetic fields together with the real-time fluorescent monitoring of multiple samples. The abovementioned properties can potentially be exploited for application in the biomedical and biosensing fields.

Convenient Route to Well-Dispersed Cu2O Nanospheres and Their Use as Photocatalysts.

A simple and facile method was developed to synthesize well-dispersed cuprous oxide nanospheres with uniform morphology and the size in the range of 400-600 nm. Cuprous oxide nanospheres were obtained through the chemical reduction of copper acetate by fructose in the presence of ethylene glycol and de-ionized water. X-ray powder diffraction (XRD), Energy dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM), UV-Vis spectroscopy (UV-Vis) and transmission electron microscopy (TEM) as well as high-resolution transmission electron microscopy (HRTEM) were used to characterize the obtained nanoparticles. The influence of time, temperature and the solvent on the formation of cuprous oxide was investigated. The growth process of cuprous oxide was analyzed and the mechanism of crystal growth was proposed. The photocatalytic activity of degradation of methyl orange (MO) under visible light irradiation was also investigated. It was found that the product of cuprous oxide had efficient catalytic for degradation MO.

Non-linear optical response by functionalized gold nanospheres: identifying design principles to maximize the molecular photo-release.

In a recent study by Voliani et al. [Small, 2011, 7, 3271], the electromagnetic field enhancement in the vicinity of the gold nanoparticle surface has been exploited to achieve photocontrolled release of a molecular cargo conjugated to the nanoparticles via 1,2,3-triazole, a photocleavable moiety. The aim of the present study is to investigate the mechanism of the photorelease by characterizing the nanoparticle aggregation status within the cells and simulating the electric field enhancement in a range of experimentally realistic geometries, such as single Au nanoparticles, dimers, trimers and random aggregates. Two plasmon-enhanced processes are examined for triazole photocleavage, i.e. three-photon excitation and third-harmonic-generation (one-photon) excitation. Taking into account the absorption cross sections of the triazole, we conclude that the latter mechanism is more efficient, and provides a photocleavage rate that explains the experimental findings. Moreover, we determine which aggregate geometries are required to maximize the field enhancement, and the dependence of such enhancement on the excitation wavelength. Our results provide design principles for maximizing the multiphoton molecular photorelease by such functionalized gold nanoparticles.

Analysis for Heat Transfer in a High Current-Passing Carbon Nanosphere Using Nontraditional Thermal Transport Model.

This paper investigates the thermal transport in hollow microscale and nanoscale spheres subject to electrical heat source using nontraditional thermal transport model. Working as supercapacitor electrodes, carbon hollow micrometer- and nanometer-sized spheres needs excellent heat transfer characteristics to maintain high specific capacitance, long cycle life, and high power density. In the nanoscale regime, the prediction of heat transfer from the traditional heat conduction equation based on Fourier's law deviates from the measured data. Consequently, the electrical heat source-induced heat transfer characteristics in hollow micrometer- and nanometer-sized spheres are studied using nontraditional thermal transport model. The effects of parameters on heat transfer in the hollow micrometer- and nanometer-sized spheres are discussed in this study. The results reveal that the heat transferred into the spherical interior, temperature and heat flux in the hollow sphere decrease with the increasing Knudsen number when the radius of sphere is comparable to the mean free path of heat carriers.

Higher-order dielectrophoresis of nonspherical particles.

Higher-order terms of dielectrophoretic (DEP) force are commonly ignored by invoking the simplifying dipole approximation. Concurrently, the trend towards micro- and nano-electrode structures in DEP design is bringing about an increasing number of instances where the approximation is expected to lose reliability. The case is severe for nonspherical particles (the shape of many biological particles) due to the shape-dependent nature of dielectric polarization. However, there is a lack of analytical means to determine multipole moments of nonspherical particles, numerical calculations of the same are regarded as unreliable, and there is a prevalence for higher-order force considerations to be ignored. As a result, the dipole approximation is used and/or nonspherical particles are approximated as spheres. This work proves the inefficacy of current qualitative criteria for the reliability of the dipole approximation and presents a quantitative substitute, with verified accuracy, that enables precise determination of the extent to which the dipole approximation would be reliable, and if found unreliable, corrects the approximation by adding second- and third-order terms of the DEP force. The effects of field nonuniformity, electrode design, and particle shape and aspect ratio on the significance of higher-order DEP forces is quantitatively analyzed. The results show that higher-order DEP forces are indeed of substantially increased significance for nonspherical particles; in the cases examined in this work, multipolar terms are seen to constitute more than 40% of the total force on ellipsoidal and cylindrical particles. It is further shown that approximating nonspherical particles as spheres of similar dimensions is subject to substantial error. Last, the substantial importance of the electrode design in influencing higher-order forces is shown.

Laser-induced cavitation in nanoemulsion with gold nanospheres for blood clot disruption: in vitro results.

Optically activated cavitation in a nanoemulsion contrast agent is proposed for therapeutic applications. With a 56°C boiling point perfluorohexane core and highly absorptive gold nanospheres at the oil-water interface, cavitation nuclei in the core can be efficiently induced with a laser fluence below medical safety limits (70 mJ/cm2 at 1064 nm). This agent is also sensitive to ultrasound (US) exposure and can induce inertial cavitation at a pressure within the medical diagnostic range. Images from a high-speed camera demonstrate bubble formation in these nanoemulsions. The potential of using this contrast agent for blood clot disruption is demonstrated in an in vitro study. The possibility of simultaneous laser and US excitation to reduce the cavitation threshold for therapeutic applications is also discussed.

Fabrication and photoactivity of a tunable-void SiO2-TiO2 core-shell structure on modified SiO2 nanospheres by grafting an amphiphilic diblock copolymer using ARGET ATRP.

SiO2-based composites have important applications in various technological fields. In this work, a tunablevoid SiO2-TiO2 core-shell structure was successfully prepared for the first time using SiO2-polymethyl methacrylate (PMMA)-polyoligo(ethylene glycol)methyl ether methacrylate (PO(EO)nMA) (n = 2, 5, and 8). An amphiphilic copolymer was used as the template, and calcination was performed using tetrabutyl titanate (TBT) as the titanium source. SiO2-PMMA-b-PO(EO)nMA microspheres were first synthesized through activators regenerated by electron transfer-atom transfer radical polymerization. Methyl methacrylate and O(EO)nMA were grafted with different EO unit numbers onto the surface of the halogen functional group of SiO2. TBT was hydrolyzed along with the PO(EO)nMA chain through hydrogen bonding, and then the SiO2-TiO2 core-shell structure was acquired through calcination to remove the polymer. Simultaneously, amorphous TiO2 crystallized during calcination. A series of characterizations indicated that the amphiphilic block copolymer was grafted onto SiO2 mesoparticle surfaces, the titania samples existed only in the anatase phase, and the prepared SiO2-TiO2 had hierarchically nanoporous structures. The gradient hydrophilicity of the PMMA-b-PO(EO)nMA copolymer template facilitated the hydrolysis of TBT molecules along the PO(EO)nMA to PMMA segments, thereby tuning the space between the core and the shell. In addition, the space was about 6 nm when the EO number was 2, and the space was about 10 nm when the EO numbers were 5 and 8. The photocatalytic activities of the SiO2-TiO2 materials were tested on the photodegradation of methyl orange.

Application of acoustic bessel beams for handling of hollow porous spheres.

Acoustic manipulation of porous spherical shells, widely used as drug delivery carriers and magnetic resonance imaging contrast agents, is investigated analytically. The technique used for this purpose is based on the application of high-order Bessel beams as a single-beam acoustic manipulation device, by which particles lying on the axis of the beam can be pulled toward the beam source. The exerted acoustic radiation force is calculated using the standard partial-wave series method, and the wave propagation within the porous media is modeled using Biot's theory of poro-elasticity. Numerical simulations are performed for porous aluminum and silica shells of different thickness and porosity. Results indicate that manipulation of low-porosity shells is possible using Bessel beams with large conical angles, over a number of broadband frequency ranges, whereas manipulation of highly porous shells can occur over both narrowband and broadband frequency domains.

Plasmon resonances and strong electric field enhancements in side-by-side tangent nanospheroid homodimers.

The plasmon resonance and electric field enhancement in a side-by-side tangent nanospheroid homodimer (TNSHD) have been investigated theoretically by using DDA and FDTD methods, respectively. The simulation results indicate that this side-by-side TNSHD has its novel optical properties. We find that the plasmon resonance with a distinct Fano lineshape can be achieved and the electric field intensity can be enhanced strongly. The tunability of the Fano resonance could provide important applications in biosensing. The obtained electric field enhancement might open a promising pathway for surface-enhanced Raman scattering (SERS) and light trapping in solar cells.

Bovine serum albumin nanospheres synchronously encapsulating "gold selenium/gold" nanoparticles and photosensitizer for high-efficiency cancer phototherapy.

Gold nanostructures have generated significant attention in biomedical areas because of their major role in cancer photothermal therapeutics. In order to conveniently combine gold nanostructures and drugs into one nanocomposite, Au2Se/Au core-shell nanostructures with strong near-infrared-absorbing properties were synthesized using a simple method and embedded inside bovine serum albumin (BSA) nanospheres by using a spray dryer equipped with an ultrasonic atomizer followed by thermal denaturation. The nanospheres with narrow size distribution mainly ranging from 450 to 600 nm were obtained. The Au2Se/Au-loaded BSA nanospheres (1 mg) adsorbed at least 0.01 mg of water-insoluble zinc phthalocyanine (ZnPc) photosensitizer. After irradiation with a 655-nm laser (20 min), the temperature of the Au2Se/Au-loaded BSA nanospheres [200 µL, 2 mg/mL, BSA/Au2Se/Au 10:1 (w/w)] increased by over 20 °C from the initial temperature of 24.82 ± 0.15 °C, and the release of ZnPc was improved compared with a corresponding sample without irradiation. After being incubated with cancer cells (human esophageal carcinoma Eca-109), the nanospheres exhibited photothermal and photodynamic therapy with a synergistic effect upon laser irradiation. This work provides novel Au2Se/Au-loaded polymer nanospheres prepared by a high-efficiency strategy for incorporating drugs for improving the efficiency in killing cancer cells.

Fabrication of nanobeads from nanocups by controlling scission/crosslinking in organic polymer materials.

The development of several kinds of micro/nanofabrication techniques has resulted in many innovations in the micro/nanodevices that support today's science and technology. With feature miniaturization, the fabrication tools have shifted from light to ionizing radiation. Here, we propose a simple micro/nanofabrication technique for organic materials using a scanning beam (SB) of ionizing radiation. By controlling the scission/crosslinking of the material via three-dimensional energy-deposition distribution of the SB, appropriate solvents can easily peel off only the crosslinked region from the bulk material. The technique was demonstrated using a focused ion beam and a chlorinated organic polymer. The polymer underwent main-chain scission upon irradiation, but it crosslinked after high-dose irradiation. Appropriate solvents could easily peel off only the crosslinked region from the bulk material. The technique, 'nanobead from nanocup', enabled the production of desired structures such as nanowires and nanomembranes. It can be also applied to the micro/nanofabrication of functional materials.

Porous carbon spheres from energetic carbon precursors using ultrasonic spray pyrolysis.

Porous carbon spheres with unique structures and morphologies are prepared from energetic carbon precursors, alkali propiolates, via ultrasonic spray pyrolysis. Aerosolized liquid droplets containing alkali propiolates act as microreactors that confine the thermal decomposition of energetic precursors and lead to the formation of several unprecedented carbon morphologies.

Rapid microwave-assisted synthesis of hierarchical ZnO hollow spheres and their application in Cr(VI) removal.

A rapid one-pot synthesis of hierarchical ZnO hollow spheres consisting of nanoparticles was realized by a facile microwave-assisted solvothermal method using ethanol as the solvent. According to the time-dependent observation of the formation process, a tentative mechanism based on ethyl acetate bubble-templating self-assembly of ZnO nanoparticles was proposed for the formation of the ZnO hollow spheres. Compared with the conventional heating, the microwave irradiation resulted in a significantly shortened reaction time (within 30 min) and considerably improved quality of the ZnO hollow spheres, such as narrower size distribution and more regular morphology, owing to the high heating rate and thus the accelerated reaction rate. It was shown that the microwave-assisted synthesis of ZnO nanostructures with tunable morphologies can be realized by judicious selection of appropriate solvents. The obtained ZnO hollow spheres exhibited an excellent adsorption capacity towards Cr(VI) ions in water because of their high surface area for adsorption and a good ability to preserve the accessible surface.

Toward optimized light utilization in nanowire arrays using scalable nanosphere lithography and selected area growth.

Vertically aligned, catalyst-free semiconducting nanowires hold great potential for photovoltaic applications, in which achieving scalable synthesis and optimized optical absorption simultaneously is critical. Here, we report combining nanosphere lithography (NSL) and selected area metal-organic chemical vapor deposition (SA-MOCVD) for the first time for scalable synthesis of vertically aligned gallium arsenide nanowire arrays, and surprisingly, we show that such nanowire arrays with patterning defects due to NSL can be as good as highly ordered nanowire arrays in terms of optical absorption and reflection. Wafer-scale patterning for nanowire synthesis was done using a polystyrene nanosphere template as a mask. Nanowires grown from substrates patterned by NSL show similar structural features to those patterned using electron beam lithography (EBL). Reflection of photons from the NSL-patterned nanowire array was used as a measure of the effect of defects present in the structure. Experimentally, we show that GaAs nanowires as short as 130 nm show reflection of <10% over the visible range of the solar spectrum. Our results indicate that a highly ordered nanowire structure is not necessary: despite the "defects" present in NSL-patterned nanowire arrays, their optical performance is similar to "defect-free" structures patterned by more costly, time-consuming EBL methods. Our scalable approach for synthesis of vertical semiconducting nanowires can have application in high-throughput and low-cost optoelectronic devices, including solar cells.