Chih-Wei Lai

Insulin‐Directed Synthesis of Fluorescent Gold Nanoclusters: Preservation of Insulin Bioactivity and Versatility in Cell Imaging

Fluorescent nanomaterials have received great attention and have been intensively studied, because of their unique optical and photophysical properties, as replacements for conventional organic dyes in optical cell imaging. Although semiconductor quantum dots show promising signals in biomedical imaging, their high inherent cytotoxicity and self-aggregation inside living cells fatally limit pragmatic biomedical applications. Fluorescent nanoclusters (NCs), in contrast, exhibit superior properties such as low toxicity and high biocompatibility. Among the various NCs, much effort has been dedicated to the study of fluorescent Au NCs. Au NCs carry quantum-mechanical properties when their sizes are comparable to or smaller than the Fermi wavelength (ca. 1 nm) of conductive electrons. The fluorescent Au NCs, with their ultrafine size, do not disturb the biological functions of the labeled bioentities; therefore, there is great potential to develop Au NCs as a new luminescent label. For example, Lin et al. successfully used water-soluble fluorescent Au NCs capped with dihydrolipoic acid (AuNC@DHLA) and modified with polyethylene glycol (PEG), bovine serum albumin (BSA), and streptavidin for cell bioimaging. Compared with organic-monolayer-protected Au NCs, the usage of proteins as a green-chemical reducing and stabilizing agent is advantageous because their complex 3D structures can withstand a wide range of pH conditions. Accordingly, Au NC synthesis with BSA and lysozyme has been reported and applied to several devices, such as nanosensors of Hg, CN , and H2O2. [12] Very recently, through the conjugation of BSA–Au NCs to folic acid, targetspecific detection of cancer-cell imaging has been demonstrated. Also, BSA–Au NCs have been applied in MDAMB-45 and HeLa tumor xenograft model imaging. Nevertheless, up to this stage, there has been a lack of reports on bioactive protein-directed fluorescent Au NCs that can still preserve their own biological role. Conversely, using Au nanoparticles encapsulated in certain enzymes, several reports claimed significant changes of enzymatic functionality. The goal of this project is thus to search for a bioactive protein to exploit as a template to direct the growth of fluorescent Au NCs. The resulting protein–Au NC nanocomposites are able to retain bioactivity, so that the associated biological role can be pursued by various imaging techniques. Among a number of proteins of vital importance, insulin is of prime interest. Insulin is a polypeptide hormone comprising only 51 amino acids. Its function primarily lies in the regulation of insulin-responsive tissues and it is also directly/indirectly related to many diseases, including diabetes, Alzheimer s disease, obesity, and aging. Its signaling pathway controls the growth of an organism, and hence exerts a profound influence on metabolism and reproduction. Herein, we report for the first time the synthesis of fluorescent Au NCs by using insulin as a template. The resulting insulin–Au NCs exhibit intense red fluorescence maximized at 670 nm and, more importantly, retain their bioactivity and biocompatibility. Several key experiments have been performed in vitro and/or in vivo to assess their viability and versatility. Detailed synthetic procedures are elaborated in the Supporting Information. In brief, by mixing insulin and HAuCl4 in Na3PO4 buffer by continuously stirring at 4 8C for 12 h, reddish luminescent insulin–Au NCs were readily prepared. The crude product was then purified by centrifugal filtration (4000g) for 30 min with a cutoff of 5 kDa to obtain the insulin–Au NCs for subsequent applications. The absorption and photoluminescence emission spectra of insulin–Au NCs are shown in Figure 1. The emission quantum yield Ff was determined to be 0.07, with observed lifetimes fitted to be 439 ns (4%) and 2041 ns (96%). The inset of Figure 1 displays a high-resolution transmission electron microscopy (HRTEM) image of insulin–Au NCs. From the respective histograms, the as-prepared insulin– Au NCs revealed a spherical shape and good size uniformity (for size distribution, see Figure S1 in the Supporting Information). The diameters of insulin–Au NCs, upon averaging over 100 particles, were calculated to be (0.92 0.03) nm (mainly for Au NCs). The hydrodynamic radii of [*] C.-L. Liu, Y.-H. Hsiao, Dr. C.-W. Lai, C.-W. Shih, Y.-K. Peng, Dr. K.-C. Tang, H.-W. Chang, Prof. P.-T. Chou Department of Chemistry, National Taiwan University 1, Section 4, Roosevelt Road, Taipei 10617 (Taiwan) Fax: (+886)2-369-5208 E-mail: chop@ntu.edu.tw

Iridium-complex-functionalized Fe3O4/SiO2 core/shell nanoparticles: a facile three-in-one system in magnetic resonance imaging, luminescence imaging, and photodynamic therapy.

Highly uniform Fe3O4/SiO2 core/shell nanoparticles functionalized by phosphorescent iridium complexes (Ir) have been strategically designed and synthesized. The Fe3O4/SiO2(Ir) nanocomposite demonstrates its versatility in various applications: the magnetic core provides the capability for magnetic resonance imaging and the great enhancement of the spin-orbit coupling in the iridium complex makes it well suited for phosphorescent labeling and simultaneous singlet oxygen generation to induce apoptosis.

Facile synthesis of highly emissive carbon dots from pyrolysis of glycerol; gram scale production of carbon dots/mSiO2 for cell imaging and drug release

We report on a facile method to synthesize carbon dots (CDs) using glycerol solvent as a single precursor via a pyrolysis process free from catalysts. This method is extremely simple and economical, and provides a feasible route for mass production of highly emissive CDs. For rationalization, a mechanism incorporating dehydration of glycerol, followed by acrylaldehyde formation is tentatively proposed for CD production. Further systematic improvement of particle homogeneity is made by harnessing the growth of CDs inside the mesoporous silica nanoparticles that act as a nano-reactor to regulate the size distribution. Simultaneously capping a polyethylene glycol (PEG)-derived reactant onto the CDs@SiO2 enhances their luminescence, stability and bio-compatibility. The as-prepared CDs@mSiO2–PEG nanocomposites are then loaded with the anti-cancer drug doxorubicin (DOX), so that the controlled release of DOX could be monitored by both time-dependent and spatially resolved ratiometric fluorescence intensity for CDs versus DOX in HeLa cells, successfully demonstrating that the CDs@mSiO2–PEG nanocomposites are suitable for cell imaging and drug release.

Potassium ion recognition by 15-crown-5 functionalized CdSe/ZnS quantum dots in H2O

Based on 15-crown-5 functionalized CdSe/ZnS quantum dots (QDs), we report a novel fluorogenic sensor to probe K+ ions in H2O; recognition of K+ can be achieved via the Förster type of energy transfer between two different color QDs, so that [K+] of the order of 10(-6) M can be promptly detected.

A New and Facile Method To Prepare Uniform Hollow MnO/Functionalized mSiO2 Core/Shell Nanocomposites

Trifunctional uniform nanoparticles comprising a manganese nanocrystal core and a functionalized mesoporous silica shell (MnO@mSiO(2)(Ir)@PEG, where Ir is an emissive iridium complex and PEG is polyethylene glycol) have been strategically designed and synthesized. The T(1) signal can be optimized by forming hollow core (H-MnO@mSiO(2)(Ir)@PEG) via a novel and facile etching process, for which the mechanism has been discussed in detail. Systematic investigation on correlation for longitudinal relaxation (T(1)) versus core shapes and shell silica porosity of the nanocomposites (MnO, H-MnO, MnO@SiO(2), MnO@mSiO(2), H-MnO@mSiO(2)) has been carried out. The results show that the worm-like nanochannels in the mesoporous silica shell not only increase water permeability to the interior hollow manganese oxide core for T(1) signal but also enhance photodynamic therapy (PDT) efficacy by enabling the free diffusion of oxygen. Notably, the H-MnO@mSiO(2)(Ir)@PEG nanocomposite with promising r(1) relaxivity demonstrates its versatility, in which the magnetic core provides the capability for magnetic resonance imaging, while the simultaneous red phosphorescence and singlet oxygen generation from the Ir complex are capable of providing optical imaging and inducing apoptosis, respectively.

Enhanced Performance and Air Stability of 3.2% Hybrid Solar Cells: How the Functional Polymer and CdTe Nanostructure Boost the Solar Cell Efficiency

A record high PCE of up to 3.2% demonstrates that the efficiency of hybrid solar cells (HSCs) can be boosted by utilizing a unique mono-aniline end group of PSBTBT-NH(2) as a strong anchor to attach to CdTe nanocrystal surfaces and by simultaneously exploiting benzene-1,3-dithiol solvent-vapor annealing to improve the charge separation at the donor/acceptor interface, which leads to efficient charge transportation in the HSCs.

Macrophage physiological function after superparamagnetic iron oxide labeling.

Our goal was to analyze the changes in morphology and physiological function (phagocytosis, migratory capabilities, humoral and cellular response, and nitric oxide secretion) of murine macrophages after labeling with a clinically used superparamagnetic iron oxide (SPIO), ferucarbotran. In SPIO‐treated macrophages, nanoparticles were taken up in the cytoplasm and accumulated in a membrane‐bound organelle. Macrophage proliferation and viability were not modified after SPIO labeling. Phagocytic function decreased after labeling with only 10 µg Fe/mL SPIO, whereas other functions including migration and production of tumor necrosis factor‐α and nitric oxide increased at the highest SPIO concentration (100 µg Fe/mL). Copyright

2D self-bundled CdS nanorods with micrometer dimension in the absence of an external directing process.

In the absence of an external direction-controlling process, exclusive self-bundled arrays of CdS nanorods are formed using a facile solution-based method involving trioctylphosphine (TOP) and tetradecylphosphonic acids (TDPA) as cosurfactants. CdS self-bundled arrays with an area of as large as 2.0 microm(2) could be obtained. A detailed mechanistic investigation leads us to conclude that the matching in nanorod concentration, intrinsic properties of CdS, and the hydrocarbon chains of the surfactants between adjacent CdS rods play key roles in the self-assembly. In sharp contrast to the defect dominant emission in solutions, the self-bundled CdS nanorods exhibit optical emission nearly free from the defect-states, demonstrating their potential for applications in luminescence and photovoltaic devices.

Mechanism of giant enhancement of light emission from Au/CdSe nanocomposites

Based on the enhanced electron–hole recombination rate generated by surface plasmon (SP) waves of Au nanoparticles (NPs) and electrons transferred from CdSe quantum dots (QDs) to Au NPs, we propose a mechanism to elucidate the luminescent behavior in Au and CdSe nanocomposites. With our proposed model, the enhancement of the spectrally integrated PL intensity can be manipulated by up to a factor of ~33, the largest value ever reported. Our study can be used to clarify the ambiguity in controlling the light emission enhancement and quenching of semiconductor nanocrystals coupled with the SP waves of metal NPs. It should be very useful for the creation of highly efficient solid-state emitters.

Syntheses and photophysical properties of type-II CdSe/ZnTe/ZnS (core/shell/shell) quantum dots

Syntheses of CdSe/ZnTe/ZnS (core/shell/shell) type-II quantum dots (QDs) are reported. Structural characterization was made via TEM, EDX, XPS and XRD. Photophysical properties were investigated via the interband emission (CdSe → ZnTe) and its associated quantum efficiency as well as relaxation dynamics. In comparison to the weak emission (Φf ∼ 4 × 10−3 in toluene) of CdSe/ZnTe (3.9/0.5 nm), capping ZnS (0.4 nm in thickness) enhances the CdSe → ZnTe interband emission by ∼30 fold (Φf ∼ 0.12), whereas the peak wavelength shifts only slightly to the red. By encapsulating dihydrolipoic acid (DHLA), water-soluble CdSe/ZnTe/ZnS QDs were also prepared, and they exhibited an interband emission at ∼930 nm with an emission yield of ∼0.1. Femtosecond pulse excitation (λex ∼ 1200 nm) measurement estimated a two-photon absorption cross section, σ, of ∼70 × 10−50 cm4 s photon−1 for DHLA-capped CdSe/ZnTe/ZnS in water, supporting its suitability for the use as near-infrared (NIR) dyes in biomedical imaging.