Shang-Wei Chou

In Vitro and in Vivo Studies of FePt Nanoparticles for Dual Modal CT/MRI Molecular Imaging

The water-solvable FePt nanoparticles of 3, 6, and 12 nm in diameter (3 nm-, 6 nm-, and 12 nm-FePt) were synthesized and applied as a dual modality contrast agent for CT/MRI molecular imaging. These nanoparticles present excellent biocompatibility and hemocompatibility in all test concentrations for the imaging contrast. The biodistribution analysis revealed the highest serum concentration and circulation half-life for 12 nm-FePt, followed by 6 nm-FePt then 3 nm-FePt. Thus, the 3 nm-FePt showed higher brain concentrations. Anti-Her2 antibody conjugated FePt nanoparticles demonstrated molecular expression dependent CT/MRI dual imaging contrast effect in MBT2 cell line and its Her2/neu gene knock out counterpart. Selective contrast enhancement of Her2/neu overexpression cancer lesions in both CT and MRI was found in tumor bearing animal after tail vein injection of the nanoparticles. The 12 nm-FePt outperformed 3 nm-FePt in both imaging modalities. These results indicate the potential of FePt nanoparticles to serve as novel multimodal molecular imaging contrast agents in clinical settings.

Synthesis of core/shell metal oxide/polyaniline nanocomposites and hollow polyaniline capsules

A double-surfactant-layer-assisted polymerization method was designed to prepare well-controlled core/shell metal oxide/polyaniline (c/s-MO/PANi) nanocomposites. Monodispersed and uniform core/shell nanocomposites including c/s-CuO/PANi, −Fe2O3/PANi, −In2O3/PANi and −Fe2O3/SiO2/PANi were successfully prepared using this polymerization method. By the removal of the cores for the resulting c/s-MO/PANi nanocomposites, hollow PANi capsules with different shapes and sizes were obtained. Our method provides a facile and effective way to design novel core/shell nanostructures with diverse functionality and high colloidal stability.

Photothermal cancer therapy via femtosecond-laser-excited FePt nanoparticles

FePt nanoparticles (NPs) have recently been revealed to be significant multifunctional materials for the applications of biomedical imaging, drug delivery and magnetic hyperthermia due to their novel magnetic properties. In this study, a newly discovered photothermal effect activated by the near infrared (NIR) femtosecond laser for FePt NPs was demonstrated. The threshold laser energy to destroy cancer cells was found to be comparable to that of gold nanorods (Au NRs) previously reported. Through the thermal lens technique, it was concluded that the temperature of the FePt NPs can be heated up to a couple of hundreds degree C in picoseconds under laser irradiation due to the excellent photothermal transduction efficiency of FePt NPs. This finding boosts FePt NPs versatility in multifunctional targeted cancer therapy.

Fluorinated thienyl-quinoxaline-based D–π–A-type copolymer toward efficient polymer solar cells: synthesis, characterization, and photovoltaic properties

A tailor-made donor–π–acceptor copolymer comprising of a medium electron-donating alkylthienyl-benzodithiophene (BDTT) moiety and a strong electron-accepting fluorinated thienyl-quinoxaline (TTFQ) segment with thiophene π-bridge units has been synthesized by Stille coupling polymerization and thoroughly characterized for use as a p-type semiconducting polymer. The semicrystalline copolymer PBDTT-TTFQ shows a broad visible-near-infrared absorption band with an optical bandgap of 1.67 eV and possesses a relatively low-lying HOMO level at −5.34 eV. In addition, the PBDTT-TTFQ neat film reveals a highly dense fibrillar nanostructure with a certain degree of long-range order, suggesting the nanoscale self-assembly of PBDTT and TTFQ segments. A bulk-heterojunction polymer solar cell based on the blend of 1 : 1 PBDTT-TTFQ:PC71BM shows an open circuit voltage of 0.75 V, a short circuit current density of 14.6 mA cm−2, and a fill factor of 56.1%, achieving a power conversion efficiency of 6.1% under the illumination of AM 1.5G, 100 mW cm−2. The results unambiguously indicate that the PBDTT-TTFQ is an auspicious candidate for next-generation solar cell materials.

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.

A Versatile Theranostic Delivery Platform Integrating Magnetic Resonance Imaging/Computed Tomography, pH/cis-Diol Controlled Release, and Targeted Therapy

The functions of biomedical imaging, cancer targeting, and controlled release of therapeutic agents were integrated into a drug delivery platform to proof its diagnostic and therapeutic capabilities. This versatile nanocomposite is based on the strategic design of wormlike mesoporous silica nanocarriers that are decorated with extremely small iron oxide nanoparticles, having a prominent T1-weighted Magnetic Resonance Imaging (MRI) signal. The controlled release function was then achieved through the grafting of polyalcohol saccharide derivative ligands onto the surfaces of mesoporous silica nanoparticles to conjugate with boronic acid functionalized gold nanoparticles, which acted as the gate and the source of computed tomography (CT) signals. This versatile platform thus exhibited a MRI/CT dual imaging property drawing on the strong points to offset the weaknesses of each, rendering more accurate diagnosis. The capping of gold nanoparticles controlled with the hydrolysis of boronate ester bonds provides the reversible opening/closing process, avoiding further release of drug once the nanocomposite leaves the cell or tissue. To endow this platform with targeting ability, protocatechuic acid was utilized as a linker to connect folic acid with the boronic acid of the gold nanoparticles. The anchor of targeting moiety, folic acid, enriched this platform and enhanced the specific cellular uptake toward cells with folate receptor. This integrated drug delivery platform was then loaded with the antitumor agent doxorubicin, demonstrating its power for targeted delivery, bioimaging, and controlled release chemotherapy to reduce the undesired side effects of chemotherapy.

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.

Direct evidence of type II band alignment in nanoscale P3HT/CdSe heterostructures

Due to inherent advantages of both constituent materials, organic/inorganic hybrid composites have attracted increasing attention. One of the fundamental issues needed to be resolved is their band alignment, which governs most of the electrical and optical properties. Here, we report the investigation of optical transition in poly(3-hexylthiophene) (P3HT)/CdSe nano-composites (NCs). It is found that the relaxation dynamics of photo-carriers in NCs is dominated by charge separation effects. Based on the band bending effect and the quantum confinement energy of electrons in the conduction band of CdSe quantum dots, we provide direct evidence of type II band alignment in P3HT/CdSe NCs. The establishment of a type II transition in NCs is very useful for the future design of efficient optoelectronic devices based on conjugated polymer/semiconductor hybrid systems.

Silver nanoprism-based paper as a ratiometric sensor for extending biothiol detection in serum

In this study, we present a selective paper-based method for the detection of L-Cys in serum using DTNB-modified Ag nanoprisms (AgP-DTNB). This method is based on the principle that L-Cys reacts with DTNB in AgP-DTNB to release a TNB2− chromophore and etches simultaneously AgP-DTNB to form Ag nanodisks, hence resulting in ratiometric changes of absorbance. Different biothiols have different affinities to etch the AgP surface and cause nanodisks of different sizes, which have slightly different resonance wavelengths. Thus, L-Cys can be discriminated with different biothiols on the basis of the different absorption spectral changes and different absorbance ratios. The linear dynamic range for the determination of L-Cys was 1–1750 μM, and the correlation coefficient (R2) was 0.9968 (y = 3.0859 × 10−4 [Cys] + 0.9376). The limit of detection for L-Cys was calculated to be 0.87 μM from 3 times the standard deviation of the blanks to the slope of the calibration curve. Compared with the other nanoparticle-based sensors in solution and on paper, AgP-DTNB possesses a much wider linear range and a comparable detection limit for L-Cys. This paper-based sensor exhibits selectivity, a wide linear sensing range, low-volume sampling, miniaturization, portability, and disposability.