Morphologically homogeneous, pH-responsive gold nanoparticles for non-invasive imaging of HeLa cancer.

Gold nanoparticles (AuNPs) have been widely used as nanocarriers in drug delivery to improve the efficiency of chemotherapy treatment and enhance early disease detection. The advantages of AuNPs include their excellent biocompatibility, easy modification and functionalization, facile synthesis, low toxicity, and controllable particle size. This study aimed to synthesize a conjugated citraconic anhydride link between morphologically homogeneous AuNPs and doxorubicin (DOX) (DOX-AuNP). The carrier was radiolabeled for tumor diagnosis using positron emission tomography (PET). The systemically designed DOX-AuNP was cleaved at the citraconic anhydride linker site under the mild acidic conditions of a cancer cell, thereby releasing DOX. Subsequently, the AuNPs aggregated via electrostatic attraction. HeLa cancer cells exhibited a high uptake of the radiolabeled DOX-AuNP. Moreover, PET tumor images were obtained using radiolabeled DOX-AuNP in cancer xenograft mouse models. Therefore, DOX-AuNP is expected to provide a valuable insight into the use of radioligands to detect tumors using PET.

Understanding metal-enhanced fluorescence and structural properties in Au@Ag core-shell nanocubes.

Au@Ag core-shell structures have received particular interest due to their localized surface plasmon resonance properties and great potential as oxygen reduction reaction catalysts and building blocks for self-assembly. In this study, Au@Ag core-shell nanocubes (Au@AgNCs) were fabricated in a facile manner via stepwise Ag reduction on Au nanoparticles (AuNPs). The size of the Au@AgNCs and their optical properties can be simply modulated by changing the Ag shell thickness. Structural characterization has been carried out by TEM, SAED, and XRD. The metal-induced fluorescence properties of probe molecules near the Au@AgNCs were measured during sedimentation of the Au@AgNCs. The unique ring-like building block of Au@AgNCs has dual optical functions as a fluorescence quencher or fluorescence enhancement medium depending on the assembled regions.

Biophysical restriction of growth area using a monodispersed gold sphere nanobarrier prolongs the mitotic phase in HeLa cells.

Gold nanoparticles are widely exploited for biological and biotechnical applications owing to their stability, biocompatibility, and known effects on cellular behaviors. Many studies have focused on nanoparticles that are internalized into cells, but extracellular nanoparticles also can regulate cell behavior, a practice known as in-plane surface nanotopography. We demonstrated that nanobarriers composed of morphologically homogeneous gold nanospheres prolonged the mitotic (M) phase in the cervical cancer cell line HeLa without inducing apoptosis. The nanobarrier was formed by electrostatic deposition of nanospheres on a negatively charged, fibronectin-coated substrate. We tested the effects of differently sized nanospheres. Gold nanospheres 42 nm in diameter were found to be non-toxic, while 111 nm nanospheres induced the production of reactive oxygen species, resulting in apoptotic cell death and arrest of cytokinesis. When exposed to sufficient 83 nm gold nanospheres to fabricate a surface nanobarrier, the M phase was delayed but cells proceeded to cytokinesis and the G1 phase. Live-cell imaging showed that the M phase increased by 2.9 h, 2.4 times longer than in control cells. Biophysical analyses indicated that this could be attributed to the specific size of the nanobarrier that physically limited the growth area around the cell.

ROS-responsive mesoporous silica nanoparticles for MR imaging-guided photodynamically maneuvered chemotherapy.

Mesoporous silica nanoparticles (MSNs) with stimuli-responsive gatekeepers have been extensively investigated for controlled drug delivery at the target sites. Herein, we developed reactive oxygen species (ROS)-responsive MSNs (R-MSNs), consisting of a gadolinium (Gd)-DOTA complex as the ROS-responsive gatekeeper and polyethylene glycol (PEG)-conjugated chlorin e6 as the ROS generator, for magnetic resonance (MR) imaging-guided photodynamic chemotherapy. Doxorubicin (DOX), chosen as an anticancer drug, was physically encapsulated into DOTA-conjugated MSNs, followed by chemical crosslinking via the addition of GdCl3. DOX-R-MSNs could effectively maintain their structural integrity in a physiological environment for 7 days and show an enhanced in vitro T1-MR imaging signal for the Gd-DOTA complex. Upon 660 nm laser irradiation, the release rate of DOX from DOX-R-MSNs remarkably increased along with the disintegration of the gatekeeper, whereas DOX release was significantly retarded without irradiation. When DOX-R-MSNs were intravenously injected into tumor-bearing mice, they were effectively accumulated in tumor tissue, which was demonstrated using MR imaging. In addition, tumor growth was significantly suppressed by DOX-R-MSNs, allowing for site-specific release of DOX in a photodynamically maneuvered manner. Overall, these results suggest that R-MSNs have potential as drug carriers for MR imaging-guided photodynamic chemotherapy.

Photofluidic Near-Field Mapping of Electric-Field Resonance in Plasmonic Metasurface Assembled with Gold Nanoparticles.

We present a near-field mapping of electric fields from the individual superspherical and ultrasmooth gold nanoparticles (AuNPs) and artificially assembled AuNP nanostructures by measuring the reconfiguration of an azobenzene-containing polymer(azo-polymer) film. Various configurations of AuNPs and the azo-polymer were studied with atomic force microscopy measurements and calculations. The interference was systematically studied with AuNP dimers of various gap distances and different embedding depth in the polymer film. Finally, we successfully demonstrated the interference of standing waves in artificially assembled plasmonic metasurface.

Assembly of "3D" plasmonic clusters by "2D" AFM nanomanipulation of highly uniform and smooth gold nanospheres.

Atomic force microscopy (AFM) nanomanipulation has been viewed as a deterministic method for the assembly of plasmonic metamolecules because it enables unprecedented engineering of clusters with exquisite control over particle number and geometry. Nevertheless, the dimensionality of plasmonic metamolecules via AFM nanomanipulation is limited to 2D, so as to restrict the design space of available artificial electromagnetisms. Here, we show that "2D" nanomanipulation of the AFM tip can be used to assemble "3D" plasmonic metamolecules in a versatile and deterministic way by dribbling highly spherical and smooth gold nanospheres (NSs) on a nanohole template rather than on a flat surface. Various 3D plasmonic clusters with controlled symmetry were successfully assembled with nanometer precision; the relevant 3D plasmonic modes (i.e., artificial magnetism and magnetic-based Fano resonance) were fully rationalized by both numerical calculation and dark-field spectroscopy. This templating strategy for advancing AFM nanomanipulation can be generalized to exploit the fundamental understanding of various electromagnetic 3D couplings and can serve as the basis for the design of metamolecules, metafluids, and metamaterials.

Zwitterionic mesoporous nanoparticles with a bioresponsive gatekeeper for cancer therapy.

UNLABELLED: To enhance cellular uptake and site-specific drug release in the tumor microenvironment, zwitterionic mesoporous silica nanoparticles (Z-MSN) were prepared by introducing a bioresponsive gatekeeper composed of negatively charged carboxylic groups and positively charged quaternary amine groups. When these Z-MSN encountered a mildly acidic environment, their surface charge readily switched from negative to positive by cleavage of an acid-labile maleic amide linkage, thus allowing for effective cellular uptake into tumor tissue. Doxorubicin (DOX) encapsulated in Z-MSN was not significantly released in physiological conditions (pH 7.4), whereas the release rate of DOX remarkably increased in mildly acidic conditions through disintegration of the gatekeeper. The antitumor efficacy of DOX-loaded Z-MSN (DOX-Z-MSN) was evaluated after their systemic administration to tumor-bearing mice. Compared to free DOX and DOX-loaded MSN without the gatekeeper, DOX-Z-MSN exhibited much higher antitumor efficacy in vivo. Overall, these results demonstrated that the hydrophilic negative surface of Z-MSN, with their closed gate, allowed for their effective accumulation in tumor tissue after systemic administration, and that their charge-swapping and gate-opening in the tumor environment enhanced their cellular uptake and drug release rate simultaneously, implying a highly promising potential for development of Z-MSN as a drug carrier for cancer therapy. STATEMENT OF SIGNIFICANCE: In an attempt to address the issues of enhanced cellular uptake and site-specific drug release of nanoparticles, we herein report on zwitterionic MSN (Z-MSN) with a pH-responsive gatekeeper which can be internalized into cancer cells via switching their surface charge from negative, in physiological conditions, to positive, in the tumor microenvironment. We hypothesized that the hydrophilic negative surface of Z-MSN with a closed gate allows for their accumulation into tumor tissue after systemic administration, whereas their charge-swapping and gate-opening in the tumor environment enhance cellular uptake and drug release rate simultaneously. Overall, Z-MSN constitute a promising drug delivery carrier for cancer therapy.

Facilitated ion diffusion in multiscale porous particles: application in battery separators.

Polyethylene (PE) separators have been the most popular option for commercial Li-ion batteries because of their uniform pore size, high tensile strength, low cost, and electrochemical stability. Unfortunately, PE separators generally suffer from significant dimensional changes at high temperatures, which frequently results in serious safety problems. In this regard, the integration of inorganic nanoparticles with PE separators has been considered to be a promising approach. Here, inorganic nanoparticles with a hierarchical pore structure were coated on a conventional polymer separator. The resultant composite separator exhibited superior Li ion transportation compared with separators coated with mesopore-only nanoparticles or conventional nonporous nanoparticles. The mesopores and macropores act synergistically to improve the electrolyte uptake and ionic conductivity of the inorganic nanoparticles, while other positive aspects such as their thermal and mechanical properties are still maintained.

Multi-functionality of macroporous TiO2 spheres in dye-sensitized and hybrid heterojunction solar cells.

Micron-sized macroporous TiO2 spheres (MAC-TiO2) were synthesized using a colloidal templating process inside emulsions, which were then coated on a nanocrystalline TiO2 light absorption film to prepare a bilayered photoanode for liquid-based dye-sensitized solar cells (DSSC) and hybrid heterojunction solid-state solar cells. MAC-TiO2 layers can enhance light scattering as well as absorption, because their pore size and periodicity are comparable to light wavelength for unique multiple scattering and a porous surface can load dye more. Moreover, due to the bicontinuous nature of macropores and TiO2 walls, electrolyte could be transported much faster in between the TiO2 spheres rather than within the small TiO2 nonporous architectures. Electron transport was also facilitated along the interconnected TiO2 walls. In DSSCs with these MAC-TiO2 scattering layers, efficiency was higher than conventional DSSCs incorporating a commercial scattering layer. The unique geometry of MAC-TiO2 results in strong improvements in light scattering and infiltration of hole-transporting materials, thereby the MAC-TiO2-based solid-state device showed comparatively higher efficiency than the device with conventional nanocrystalline TiO2.

Optimizing control of Fe catalysts for carbon nanotube growth.

One must control the size distribution of catalyst Fe nano-particles (NPs) very carefully if one is to have any chance of growing "super-aligned" carbon nanotube (CNT) forests which can be spun directly into yarns and pulled directly into long sheets. Control of the Fe Nps size is important during all phases, including: the catalyst deposition, annealing and forest growth. As a result, it is important to understand how NPs are affected by various experimental factors as well as how those catalyst NPs then cause the growth of the forests. This paper focuses on two key experimental factors: The as-deposited thickness of the Fe catalyst film and the use of hydrogen gas (H2) during anneal and growth. We found that the sheet resistance (Rs) of as-deposited Fe films is directly related to the average film thickness and can be used to estimate whether the films can catalyze the growth of super-aligned forests. The height of the CNT forests decrease with decreasing Rs, but only slowly. More importantly, CNTs grown on the largest and the smallest Rs films are less aligned. Instead, they are more curled and wavy due to the Fe NP dynamics. The use of Hydrogen (H2) affects the formation of Fe NPs from the as-deposited film as well as their composition during the forest growth. We find that the addition of H2 to a CNT forest growth process at 680 degrees C (C2H2/He [30/600 sccm]) increases the CNT alignment substantially. H2 can also reduce iron-oxides which otherwise would impede the formation of NPs. As a result, H2 has multiple roles: besides its chemical reactivity, H2 is important for catalyst reconstruction into NPs having a proper size distribution as well as surface density.

Gold-decorated block copolymer microspheres with controlled surface nanostructures.

Gold-decorated block copolymer microspheres (BCP-microspheres) displaying various surface morphologies were prepared by the infiltration of Au precursors into polystyrene-b-poly(4-vinylpyridine) (PS-b-P4VP) microspheres. The microspheres were fabricated by emulsifying the PS-b-P4VP polymers in chloroform into a surfactant solution in water, followed by the evaporation of chloroform. The selective swelling of the P4VP domains in the microspheres by the Au precursor under acidic conditions resulted in the formation of Au-decorated BCP-microspheres with various surface nanostructures. As evidenced by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) measurements, dotted surface patterns were formed when microspheres smaller than 800 nm were synthesized, whereas fingerprint-like surface patterns were observed with microspheres larger than 800 nm. Au nanoparticles (NPs) were located inside P4VP domains near the surfaces of the prepared microspheres, as confirmed by TEM. The optical properties of the BCP-microspheres were characterized using UV-vis absorption spectroscopy and fluorescence lifetime measurements. A maximum absorption peak was observed at approximately 580 nm, indicating that Au NPs are densely packed into P4VP domains on the microspheres. Our approach for creating Au-NP-hybrid BCP-microspheres can be extended to other NP systems such as iron-oxide or platinum NPs. These precursors can also be selectively incorporated into P4VP domains and induce the formation of hybrid BCP-microspheres with controlled surface nanostructures.