Kuo Chu Hwang

Designing Multi-Branched Gold Nanoechinus for NIR Light Activated Dual Modal Photodynamic and Photothermal Therapy in the Second Biological Window

Gold nanoechinus can sensitize the formation of singlet oxygen in the first and the second near-infra red (NIR) biological windows and exert in vivo dual modal photodynamic and photothermal therapeutic effects (PDT and PTT) to destruct the tumors completely. This is the first literature example of the destruction of tumors in NIR window II induced by dual modal nanomaterial-mediated photodynamic and photothermal therapy (NmPDT & NmPTT).

Carbon Nanoparticle-Enhanced Immunoelectrochemical Detection for Protein Tumor Marker with Cadmium Sulfide Biotracers

We have developed a sensitive electrochemical immunoassay system for the detection of a protein tumor marker, carcinoembryonic antigen (CEA), that is based on a carbon nanoparticle (CNP)/poly(ethylene imine) (PEI)-modified screen-printed graphite electrode (CNP-PEI/SPGE) covered with anti-CEA antibodies. The signal amplification strategy--using CdS nanocrystals as biotracers and CNPs to enhance electron transfer--improves the sensitivity and detection limit for CEA, suggesting that this system holds promise for development into a point-of-care or disposable home-care self-diagnostic tool. This biosensor is based on a sandwich complex immunoassay, which we assembled from sequential layers of the anti-CEA antibody (alphaCEA) on CNP-PEI/SPGE, the CEA sample, and the CdS nanocrystal quantum dots (QDs) sensitized with alphaCEA (alphaCEA-CdS QD). We used square wave anodic stripping voltammetry (SWASV) to amplify the signal current response obtained from the dissolved alphaCEA-CdS QDs. The calibration curve for CEA concentration was linear in the range of 0.032-10 ng/mL; the detection limit (estimated as the mean of the blank sample plus three times the standard deviation obtained on the blank sample) was 32 pg/mL (equivalent to 160 fg in a 5 microL sample). This method is suitably precise and sensitive to function as a means of determining urinary CEA, which is a better marker than serum CEA for the early detection of urothelial carcinoma.

Preparation of Fluorescent Magnetic Nanodiamonds and Cellular Imaging

Magnetic nanodiamonds were prepared via solid-state microwave arcing of a nanodiamond-ferrocene mixed powder in a focused microwave oven. High-resolution transmission electron microscope (HRTEM) images show that a magnetic nanodiamond is composed of iron nanoparticles encapsulated by graphene layers on the surface of nanodiamonds. Fluorescence property was introduced onto magnetic nanodiamonds by chemical modification of magnetic nanodiamonds via surface grafting of poly(acrylic acids) and fluorescein o-methacrylate. Fluorescent magnetic nanodiamonds are water soluble with a solubility of approximately 2.1 g/L. Cellular-imaging experiments show that fluorescent magnetic nanodiamonds could be ingested by HeLa cells readily in the absence of agonist (i.e., folate) moieties on the surface of nanodiamonds.

Metal Nanoparticles Sensitize the Formation of Singlet Oxygen

Singlet oxygen (O2) is known to play an indispensible role in the photodynamic therapy (PDT) treatment of cancer, and is an important oxidant for hydroperoxidation of olefins in organic synthesis. Singlet O2 is conventionally formed by sensitization by organic photosensitizers, such as Rose Bengal, silicon phthalocyanine, etc. These organic or organometallic dyes are, however, prone to photoinduced degradation and enzymatic degradation, which becomes problematic in PDT treatments, and reduces the efficiency of the generation of singlet O2. [5,8] It is, therefore, important to search for photosensitizers with highly efficient singlet O2 generation and large absorption coefficients that are photochemically more stable and less prone to enzymatic degradation. Previously, it was reported that the yield of singlet oxygen production by a photosensitizer, namely, Rose Bengal, was enhanced by a silver island film through the metal-enhanced absorption of photosensitizer. It was also reported that a gold nanodisk could enhance the phosphorescence decay rate of singlet oxygen, leading to a larger characteristic phosphorescence emission band of singlet oxygen at 1270 nm. In another two studies, it was observed that the quantum yield of singlet O2 formation generated by phthalocyanine photosensitizers can be enhanced by the presence of gold nanoparticles. Herein we report an unprecedented observation that singlet oxygen can be formed through direct sensitization by metal nanoparticles (M NPs, M=Ag, Pt, and Au) without the presence of any organic photosensitizers. Unambiguous experimental evidence includes direct observation of singlet oxygen emission at roughly 1268 nm, hydroperoxidation of cyclohexene, green fluorescence from a selective singlet oxygen fluorescent sensor, namely, Singlet Oxygen Sensor Green (SOSG, Molecular Probe), and quenching of singlet oxygen phosphorescence by sodium azide. As shown in Figure 1, photoexcitation of M NPs at the surface plasmon resonance absorption bands of Ag (d= 55, 42 nm), Pt (10 nm), and Au (22 nm) in D2O results in characteristic singlet oxygen emission at 1264 and 1268 nm, respectively. Control experiments show that in the absence of metal nanoparticles, photoexcitation of poly(vinyl pyrrolidone (PVP) in D2O using either 254 or 508 nm light did not result in any detectable singlet O2 emission signal (see the

First Demonstration of Gold Nanorods‐Mediated Photodynamic Therapeutic Destruction of Tumors via Near Infra‐Red Light Activation

Previously, a large volume of papers reports that gold nanorods (Au NRs) are able to effectively kill cancer cells upon high laser doses (usually 808 nm, 1-48 W/cm²) irradiation, leading to hyperthermia-induced destruction of cancer cells, i.e, photothermal therapy (PTT) effects. Combination of Au NRs-mediated PTT and organic photosensitizers-mediated photodynamic therapy (PDT) were also reported to achieve synergistic PTT and PDT effects on killing cancer cells. Herein, we demonstrate for the first time that Au NRs alone can sensitize formation of singlet oxygen (¹O₂) and exert dramatic PDT effects on complete destrcution of tumors in mice under very low LED/laser doses of single photon NIR (915 nm, <130 mW/cm²) light excitation. By changing the NIR light excitation wavelengths, Au NRs-mediated phototherapeutic effects can be switched from PDT to PTT or combination of both. Both PDT and PTT effects were confirmed by measurements of reactive oxygen species (ROS) and heat shock protein (HSP 70), singlet oxygen sensor green (SOSG) sensing, and sodium azide quenching in cellular experiments. In vivo mice experiments further show that the PDT effect via irradiation of Au NRs by 915 nm can destruct the B16F0 melanoma tumor in mice far more effectively than doxorubicin (a clinically used anti-cancer drug) as well as the PTT effect (via irradiation of Au NRs by 780 nm light). In addition, we show that Au NRs can emit single photon-induced fluorescence to illustrate their in vivo locations/distribution.

Photosensitization of Singlet Oxygen and In Vivo Photodynamic Therapeutic Effects Mediated by PEGylated W18O49 Nanowires

Upon excitation with near-infrared light (980 nm), PEGylated W18 O49 nanowires can sensitize the formation of singlet oxygen and thus reactive oxygen species (ROS). The resulting photodynamic therapy (PDT) effect can cause the destruction of tumors in the absence of organic photosensitizers. PEG=poly(ethylene glycol), PTT=photothermal therapy.

Facile surface functionalization of nanodiamonds.

Nanodiamonds (NDs) have versatile applications in electro-optical devices, sensors, and biomedicine. Owing to the difficulty in activation of the inert sp(3) C-H bonds on the surface of NDs, it is not trivial to modify the surface functionalities on NDs. A few functionalization methods have been reported in the literature for surface modification of NDs. Many of them, however, are either multiple steps/time-consuming, or require the use of highly toxic/environmentally unfriendly reagents, such as fluorine gas and sulfuric acid. It is necessary to develop a simple process for surface functionalization of NDs to have both hydrophobic and hydrophilic functional groups. In this report, a facile process was developed to allow easy and rapid surface modification of NDs to become dispersible in either water or organic solvents using the same process. The process involves surface graphitization of NDs, followed by radical initiated surface grafting of oligomers with various functionalities, including -C(=O)OCH(3), -COOH, -NH(2), or aliphatic moieties.

Visible-light initiated copper(I)-catalysed oxidative C–N coupling of anilines with terminal alkynes: one-step synthesis of α-ketoamides

Development of C–N coupling processes is fundamentally important and challenging for the synthesis of biologically active molecules and drugs. Herein, we report a highly atom efficient green process for the synthesis of α-ketoamides via visible-light induced copper(I) chloride catalysed direct oxidative Csp–N coupling reactions using commercially available alkynes and anilines at room temperature without the use of hazardous chemicals and harsh reaction conditions. Forty-seven examples are presented using a broad range of substrates including electron deficient anilines and various terminal alkynes. The current photochemical process is able to achieve epoxide hydrolase inhibitors in one step with high yield (92–95%). This transformation is highly efficient and highly selective for the synthesis of α-ketoamides.

Photoinduced Copper-Catalyzed Regioselective Synthesis of Indoles: Three-Component Coupling of Arylamines, Terminal Alkynes, and Quinones

The first successful example of a visible-light-induced copper-catalyzed process for C-H annulation of arylamines with terminal alkynes and benzoquinone is described. This three-component reaction allows use of a variety of commercial terminal alkynes as coupling partners for the one-step regioselective synthesis of functionalized indoles. Moreover, the current process represents a sustainable and atom-economical approach for the preparation of complex indoles from easily accessible starting materials under visible-light irradiation, without the need for expensive metals and harsh reaction conditions.

Cancer cell labeling and tracking using fluorescent and magnetic nanodiamond

Nanodiamond, a promising carbon nanomaterial, develops for biomedical applications such as cancer cell labeling and detection. Here, we establish the nanodiamond-bearing cancer cell lines using the fluorescent and magnetic nanodiamond (FMND). Treatment with FMND particles did not significantly induce cytotoxicity and growth inhibition in HFL-1 normal lung fibroblasts and A549 lung cancer cells. The fluorescence intensities and particle complexities were increased in a time- and concentration-dependent manner by treatment with FMND particles in lung cancer cells; however, the existence of FMND particles inside the cells did not alter cellular size distribution. The FMND-bearing lung cancer cells could be separated by the fluorescent and magnetic properties of FMNDs using the flow cytometer and magnetic device, respectively. The FMND-bearing cancer cells were identified by the existence of FMNDs using flow cytometer and confocal microscope analysis. More importantly, the cell morphology, viability, growth ability and total protein expression profiles in the FMND-bearing cells were similar to those of the parental cells. The separated FMND-bearing cells with various generations were cryopreservation for further applications. After re-thawing the FMND-bearing cancer cell lines, the cells still retained the cell survival and growth ability. Additionally, a variety of human cancer types including colon (RKO), breast (MCF-7), cervical (HeLa), and bladder (BFTC905) cancer cells could be used the same strategy to prepare the FMND-bearing cancer cells. These results show that the FMND-bearing cancer cell lines, which reserve the parental cell functions, can be applied for specific cancer cell labeling and tracking.