Yung-Kang Peng

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

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.

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.

Superiority of Branched Side Chains in Spontaneous Nanowire Formation: Exemplified by Poly(3-2-methylbutylthiophene) for High-Performance Solar Cells

One-dimensional nanostructures containing heterojunctions by conjugated polymers, such as nanowires, are expected to greatly facilitate efficient charge transfer in bulk-heterojunction (BHJ) solar cells. Thus, a combined theoretical and experimental approach is pursued to explore spontaneous nanowire formation. A dissipative particle dynamics simulation is first performed to study the morphologies formed by rodlike polymers with various side-chain structures. The results surprisingly predict that conjugated polymers with branched side chains are well suited to form thermodynamically stable nanowires. Proof of this concept is provided via the design and synthesis of a branched polymer of regioregular poly(3-2-methylbutylthiophene) (P3MBT), which successfully demonstrates highly dense nanowire formation free from any stringent conditions and stratagies. In BHJ solar cells fabricated using a blend of P3MBT and [6,6]-phenyl-C71-butyric acid methyl ester (PC(71) BM), P3MBT polymers are self-organized into highly crystalline nanowires with a d(100) spacing of 13.30 Å. The hole mobility of the P3MBT:PC(71) BM (1:0.5 by weight) blend film reaches 3.83 × 10(-4) cm(2) V(-1) s(-1) , and the maximum incident photon-to-current efficiency reaches 68%. The results unambiguously prove the spontaneous formation of nanowires using solution-processable conjugated polymers with branched alkyl side chains in BHJ solar cells.

Antiferromagnetic iron nanocolloids: a new generation in vivo T1 MRI contrast agent.

A novel T1 agent, antiferromagnetic α-iron oxide-hydroxide (α-FeOOH) nanocolloids with a diameter of 2-3 nm, has been successfully prepared. These nanocolloids, together with a post synthetic strategy performed in mesoporous silica, are a great improvement over the low T1-weighted contrast common in traditional magnetic silica nanocomposites. The intrinsic antiferromagnetic goethite (α-FeOOH) shows very low magnetization (M(z)) of 0.05 emu g(-1) at H = 2 T at 300 K (0.0006 emu g(-1) for FeOOH/WMSN-PEG), which is 2 orders of magnitude smaller than any current ultrasmall iron oxide NPs (>5 emu g(-1)) reported to date, hence ensuring the low r2 (∝ Mz) (7.64 mM(-1) s(-1)) and r2/r1 ratio (2.03) at 4.7 T. These biodegradable α-FeOOH nanocolloids also demonstrate excellent in vitro cellular imaging and in vivo MR vascular and urinary trace imaging capability with outstanding biocompatibility, which is exceptionally well secreted by the kidney and not the liver as with most nanoparticles, opening up a new avenue for designing powerful antiferromagnetic iron T1 contrast agents.

Trimethylphosphine-Assisted Surface Fingerprinting of Metal Oxide Nanoparticle by 31P Solid-State NMR: A Zinc Oxide Case Study

Nano metal oxides are becoming widely used in industrial, commercial and personal products (semiconductors, optics, solar cells, catalysts, paints, cosmetics, sun-cream lotions, etc.). However, the relationship of surface features (exposed planes, defects and chemical functionalities) with physiochemical properties is not well studied primarily due to lack of a simple technique for their characterization. In this study, solid state (31)P MAS NMR is used to map surfaces on various ZnO samples with the assistance of trimethylphosphine (TMP) as a chemical probe. As similar to XRD giving structural information on a crystal, it is demonstrated that this new surface-fingerprint technique not only provides qualitative (chemical shift) but also quantitative (peak intensity) information on the concentration and distribution of cations and anions, oxygen vacancies and hydroxyl groups on various facets from a single deconvoluted (31)P NMR spectrum. On the basis of this technique, a new mechanism for photocatalytic •OH radical generation from direct surface-OH oxidation is revealed, which has important implications regarding the safety of using nano oxides in personal care products.

One-Step, Room-Temperature Synthesis of Glutathione-Capped Iron-Oxide Nanoparticles and their Application in In Vivo T1-Weighted Magnetic Resonance Imaging

The room-temperature, aqueous-phase synthesis of iron-oxide nanoparticles (IO NPs) with glutathione (GSH) is reported. The simple, one-step reduction involves GSH as a capping agent and tetrakis(hydroxymethyl)phosphonium chloride (THPC) as the reducing agent; GSH is an anti-oxidant that is abundant in the human body while THPC is commonly used in the synthesis of noble-metal clusters. Due to their low magnetization and good water-dispersibility, the resulting GSH-IO NPs, which are 3.72 ± 0.12 nm in diameter, exhibit a low r2 relaxivity (8.28 mm(-1) s(-1)) and r2/r1 ratio (2.28)--both of which are critical for T1 contrast agents. This, together with the excellent biocompatibility, makes these NPs an ideal candidate to be a T1 contrast agent. Its capability in cellular imaging is illustrated by the high signal intensity in the T1-weighted magnetic resonance imaging (MRI) of treated HeLa cells. Surprisingly, the GSH-IO NPs escape ingestion by the hepatic reticuloendothelial system, enabling strong vascular enhancement at the internal carotid artery and superior sagittal sinus, where detection of the thrombus is critical for diagnosing a stroke. Moreover, serial T1- and T2-weighted time-dependent MR images are resolved for a rats kidneys, unveiling detailed cortical-medullary anatomy and renal physiological functions. The newly developed GSH-IO NPs thus open a new dimension in efforts towards high-performance, long-circulating MRI contrast agents that have biotargeting potential.

Comprehensive study of medium-bandgap conjugated polymer merging a fluorinated quinoxaline with branched side chains for highly efficient and air-stable polymer solar cells

A new medium-bandgap conjugated copolymer comprising a rigidly fused benzo[1,2-b:4,5-b′]-dithiophene (BDT) unit and a fluorinated quinoxaline moiety through a thiophene π-spacer has been rationally designed and synthesized by Stille coupling polymerization and thoroughly evaluated for use as a donor material in bulk-heterojunction polymer solar cells (BHJ PSCs). A comprehensive study of the structure-function relationship in the PSCs was also explored. The PDBTQEH copolymer exhibits good solubility in a wide range of organic solvents and has a high hole mobility. Introduction of an highly electronegative fluorine atoms to quinoxaline moiety further lowers both the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energy levels of polymer, which is beneficial for attaining higher open-circuit voltage (Voc) and long-term stability. Conventional architecture BHJ PSCs using PBDTQEH:PC71BM (1 : 1, w/w) displays a high power conversion efficiency (PCE) of 5.90%. Compared with the same composition, the device in the inverted configuration reveals a rather high PCE of 6.36% with a Voc of 0.78 V, a short-circuit current density (Jsc) of 12.72 mA cm−2, and a high fill factor (FF) of 64.3%. The inverted device also demonstrates outstanding air stability; without any encapsulation, the solar efficiency of the device remains above 74% of the original value after storage in air for 1000 h.

Importance of the structural integrity of a carbon conjugated mediator for photocatalytic hydrogen generation from water over a CdS–carbon nanotube–MoS2 composite

Incorporation of CdS quantum dots is shown to significantly promote photocatalytic hydrogen production from water over single-layer MoS2 in a remote manner via their dispersions on a carbon nanotube as a nanocomposite: the hydrogen evolution rate is found to be critically dependent on the content and structural integrity of the carbon nanotube such that the double-walled carbon nanotube shows superior H2 production to a single-walled carbon nanotube because the inner carbon tubules survive from the structural damage during functionalization.