Henry Du

Gold Nanoparticle-Enhanced and Size-Dependent Generation of Reactive Oxygen Species from Protoporphyrin IX

Photosensitizer, protoporphyrin IX (PpIX), was conjugated with Au nanoparticles (Au NPs) of 19, 66, and 106 nm diameter to study the size-dependent enhancement of reactive oxygen species (ROS) formation enabled by Au NPs. The ROS enhancement ratio is determined to be 1:2.56:4.72 in order of increasing Au NP size, in general agreement with theoretically calculated field enhancement to the fourth power. The convergence of the experimental and simulated results suggests that Au NP-enhanced and size-dependent ROS formation can be attributed directly to the localized electromagnetic field as a result of surface plasmonic resonance of Au NPs under light irradiation. In vitro study on the ROS formation enabled by PpIX-conjugated Au NPs in human breast cancer cells (MDA-MB-231) revealed the similar size-dependent enhancement of intracellular ROS formation, while the enhancement greatly depended on cellular uptake of Au NPs. Cellular photodynamic therapy revealed that cell destruction significantly increased in the presence of Au NPs. Compared to the untreated control (0% destruction), 22.6% cell destruction was seen in the PpIX alone group and more than 50% cell destruction was obtained for all PpIX-conjugated Au NPs. The 66 nm Au NPs yielded the highest cell destruction, consistent with the highest cellular uptake and highest ROS formation. Clearly, the complex cellular environment, size-dependent cellular uptake of Au NPs, and ROS generations are vital contributors to the overall cellular PDT efficacy.

Effect of Oxidation on Surface-Enhanced Raman Scattering Activity of Silver Nanoparticles: A Quantitative Correlation

We quantitatively studied, using X-ray photoelectron spectroscopy (XPS), oxidation of substrate-immobilized silver nanoparticles (Ag NPs) in a wide range of conditions, including exposure to ambient air and controlled ozone environment under UV irradiation, and we correlated the degree of silver oxidation with surface-enhanced Raman scattering (SERS) enhancement factors (EFs). The SERS activity of pristine and oxidized Ag NPs was assessed by use of trans-1,2-bis(4-pyridyl)ethylene (BPE) and sodium thiocynate as model analytes at the excitation wavelength of 532 nm. Our study showed that the exposure of Ag NPs to parts per million (ppm) level concentrations of ozone led to the formation of Ag(2)O and orders of magnitude reduction in SERS EFs. Such an adverse effect was also notable upon exposure of Ag NPs under ambient conditions where ozone existed at parts per billion (ppb) level. The correlated XPS and SERS studies suggested that formation of just a submonolayer of Ag(2)O was sufficient to decrease markedly the SERS EF of Ag NPs. In addition, studies of changes in plasmon absorption bands pointed to the chemical enhancement as a major reason for deterioration of SERS signals when substrates were pre-exposed to ambient air, and to a combination of changes in chemical and electromagnetic enhancements in the case of substrate pre-exposure to elevated ozone concentrations. Finally, we also found UV irradiation and ozone had a synergistic effect on silver oxidation and thus a detrimental effect on SERS enhancement of Ag NPs and that such oxidation effects were analyte-dependent, as a result of inherent differences in chemical enhancements and molecular binding affinities for various analytes.

SERS Not To Be Taken for Granted in the Presence of Oxygen

Oxidation of the Ag nanoparticle surface has a dramatic effect on the adsorption, orientation, and SERS detection limit of nitroaromatic molecules in aqueous solutions. Ultrasensitive SERS detection of p-nitrophenol can be achieved when oxidation of surface-immobilized Ag nanoparticles is inhibited by replacing the oxygen dissolved in water with argon gas. The presence of silver oxide at the nanoparticle surface hinders charge transfer between the aromatic ring and the underlying Ag metal surface and drastically decreases the overall detection sensitivity.

5-aminolevulinic acid-conjugated gold nanoparticles for photodynamic therapy of cancer.

BACKGROUND Effective delivery of photosensitizer to target tumor cells that causes minimal damage to healthy cells is an important requirement in photodynamic therapy of cancer. AIM We aimed to use biocompatible gold nanoparticles as a vehicle to deliver 5-aminolevulinic (5-ALA) acid for selective and efficient photodynamic therapy. RESULTS Protoporphyrin IX accumulated preferentially in fibrosarcoma tumor cells treated with 5-ALA-conjugated nanoparticles while yielding significantly higher reactive oxygen species compared with that with 5-ALA. The elevation of reactive oxygen species resulted in 50% more cytotoxicity to tumor cells than that of 5-ALA alone. Selective destruction of tumor cells was also achieved using 5-ALA-conjugated nanoparticles in co-culture with dermal fibroblasts. CONCLUSIONS 5-ALA-conjugated nanoparticles offer a new modality for selective and efficient destruction of tumor cells, with minimal damage to fibroblasts in the 5-ALA-photodynamic therapy.

Towards Full-Length Accumulative Surface-Enhanced Raman Scattering-Active Photonic Crystal Fibers

The integration of microfluidics with photonics on a single platform using well-established planar device technology has led to the emergence of the exciting field of optofluidics. As both a light guide and a liquid/gas transmission cell, photonic crystal fiber (PCF, also termed microstructured or holey fiber), synergistically combines microfluidics and optics in a single fiber with unprecedented light path length not readily achievable using planar optofluidics. PCF, an inherent optofluics platform, offers excellent prospects for a multitude of scientific and technological applications. The accessibility to the air channels of PCF has also opened up the possibility for functionalization of the channel surfaces (silica in nature) at the molecular and the nanometer scales, in particular to impart the functionality of surface-enhanced Raman scattering (SERS) in PCF for sensing and detection. SERS, an ever advancing research field since its discovery in the 1970s, has tremendous potential for label-freemolecular identification at trace or even single-molecule levels due to up to 10 increase in the Raman scattering cross-section of a molecule in the presence of Ag or Au nanostructures. Seminal work has been reported on the development of 1D and 2D SERS substrates for a variety of sensing applications. The use of 3D geometry, i.e., substrates obtained by the deposition of noble nanoparticles onto porous silicon or porous aluminum membrane offered additional advantages of increased SERS intensity due to increased SERS probing area, as well as the membrane waveguiding properties. Specifically, several orders of magnitude higher SERS intensity, affording picoor zeptogram-level detection of explosives, has been demonstrated with porous alumina membranes containing 60-mm-long nanochannels, as compared to a solid planar substrate. SERS-active PCF optofluidics, as a special fiber optic SERS platform, offers easy system integration for in situ flow-through detection, and, more importantly, much longer light interaction length with analyte, thus promising to open a new vista in chemical/biological sensing, medical diagnosis, and process monitoring, especially in geometrically confined or sampling volume-limited systems. Various attempts have been made over the last several years to integrate SERS with the PCF platform by incorporating Ag or Au nanostructures albeit inside a very limited segment (typically a few centimeters) of the fiber air channels. Examples include deposition of Ag particulates and thin films by chemical vapor deposition at high pressure or coating of Ag and Au nanoparticles using colloidal solutions driven into the microscopic air channels via capillary force with backscattering as the typical data acquisition mode. Building uniform SERS functionality throughout the length of the PCF while preserving its light guide characteristics has remained elusive as measured Raman intensity is a combination of the accumulative gain from Raman scattering and the continuous loss from nanoparticle-induced light attenuation over the path length. As a result, we have recommended and recently described in a brief study forward scattering as a more suitable detection mode to unambiguously assess the SERS-active nature of PCF. To the best of our knowledge, this article is the first report of net accumulative SERS from the full-length Ag-nanoparticlefunctionalized PCFs. The finding has been enabled by a fine control of the coverage density of Ag nanoparticles and studies of a competitive interplay between SERS gain and light attenuation in the Raman intensity with PCFs of varying length. Using two different types of PCF, i.e., solid-core PCF and hollow-core PCF, we show that Raman gain in PCF prevails at relatively low nanoparticle coverage density (below 0.5 particlemm ), allowing full benefit of accumulation of Raman intensity along the fiber length for robust SERS sensing and enhanced measurement sensitivity. Light attenuation dominates at higher nanoparticle coverage density, however, diminishing the path-length benefit. Shown in Figure 1 are cross-sectional scanning electron microscopy (SEM) images of solid-core PCFand hollow-core PCF used in this work. Also depicted in the figure is the light-guide process in the corresponding PCFs that contain immobilized Ag nanoparticles and are filled with aqueous solution throughout the cladding air channels for solid-core PCFand in the center air core only for hollow-core PCF. Note that light is guided via total internal reflectance in both cases. The presence of the aqueous solution in the cladding air channels does not fundamentally change the contrast of the higher index silica core and the lower index liquid-silica cladding in the solid-core PCF. The selective

Long-period gratings in photonic crystal fiber as an optofluidic label-free biosensor.

Using long-period gratings (LPG) inscribed in photonic crystal fiber (PCF) and coupling this structure with an optically aligned flow cell, we have developed an optofluidic refractive index transduction platform for label-free biosensing. The LPG-PCF scheme possesses extremely high sensitivity to the change in refractive index induced by localized binding event in different solution media. A model immunoassay experiment was carried out inside the air channels of PCF by a series of surface modification steps in sequence that include adsorption of poly(allylamine hydrochloride) monolayer, immobilization of anti-rat bone sialoprotein monoclonal primary antibody, and binding interactions with non-specific goat anti-rabbit IgG (H+L) and specific secondary goat anti-mouse IgG (H+L) antibodies. These adsorption and binding events were monitored in situ using the LPG-PCF by measuring the shift of the core-to-cladding mode coupling resonance wavelength. Steady and significant resonance changes, about 0.75 nm per nanometer-thick adsorbed/bound bio-molecules, have been observed following the sequence of the surface events with monolayer sensitivity, suggesting the promising potential of LPG-PCF for biological sensing and evaluation.

Long-period gratings inscribed in air- and water-filled photonic crystal fiber for refractometric sensing of aqueous solution

We report a comparative study of inscription of long-period gratings (LPGs) in air- and water-filled photonic crystal fiber (PCF) via residual stress relaxation using a scanning CO2 laser for refractometric sensing. Under the same inscribing condition, LPGs fabricated following the two PCF schemes exhibit different resonance spectral features. Using NaCl aqueous solution of various concentrations, we demonstrate that both PCF-LPGs possess excellent sensitivity of ∼10−7 refractive index unit within the index range of 1.33 and 1.35, whereas LPGs inscribed in water-filled PCF show much narrower full width at half maximum in the resonance spectrum.

Structure fits the purpose: photonic crystal fibers for evanescent-field surface-enhanced Raman spectroscopy

We report numerical simulation and hyperspectral Raman imaging of three index-guiding solid-core photonic crystal fibers (PCFs) of different air-cladding microstructures to assess their respective potential for evanescent-field Raman spectroscopy, with an emphasis on achieving surface-enhanced Raman scattering (SERS) over the entire fiber length. Suspended-core PCF consisting of a silica core surrounded by three large air channels conjoined by a thin silica web is the most robust of the three SERS-active PCFs, with a demonstrated detection sensitivity of 1x10(-10) M R6G in an aqueous solution of only approximately 7.3 microL sampling volume.

Design of solid-core microstructured optical fiber with steering-wheel air cladding for optimal evanescent-field sensing

We present the design of a solid-core microstructured optical fiber with steering-wheel pattern of large holes in cladding as platform for evanescent-field sensing. Both geometry and optical properties of the fiber are numerical computed and analyzed in consideration of manufacturability using sol-gel casting technique as well as by evaluating a triangular lattice of holes with three rings in the design structure so that effective parameters can be established using effective step-index model. We predict less than 0.7 dB/m confinement loss at 850 nm, 29%, 13.7%, and 7.2% of light intensity overlap in air holes at 1500 nm, 1000 nm, and 850 nm wavelength, respectively, in such fiber. With the low loss and high mode-field overlap, the steering-wheel structured fiber is well suited for evanescent-field sensing and detection of chemical and biological species.

Differential SERS activity of gold and silver nanostructures enabled by adsorbed poly(vinylpyrrolidone).

We report that poly(vinylpyrrolidone) (PVP), a common stabilizer of colloidal dispersions of noble metal nanostructures, has a dramatic effect on their surface-enhanced Raman scattering (SERS) activity and enables highly selective SERS detection of analytes of various type and charge. Nanostructures studied include PVP-stabilized Au-Ag nanoshells synthesized by galvanic exchange reaction of citrate-reduced Ag nanoparticles (NPs), as well as solid citrate-reduced Ag and Au NPs, both before and after stabilization with PVP. All nanostructures were characterized in terms of their size, surface plasmon resonance wavelength, surface charge, and chemical composition. While the SERS activities of the parent citrate-reduced Ag and Au NPs are similar for rhodamine 6G (R6G) and 1,2-bis(4-pyridyl)ethylene (BPE) at various pH values, PVP-stabilized nanostructures demonstrate large differences in SERS enhancement factors (EFs) between these analytes depending on their chemical nature and protonation state. At pH values higher than BPEs pK(a2) of 5.65, where the analyte is largely unprotonated, the PVP-coated Au-Ag nanoshells showed a high SERS EF of >10(8). In contrast, SERS EFs were 10(3)- to 10(5)-fold lower for the protonated form of BPE at lower pH values, or for the usually highly SERS-active cationic R6G. The differential SERS activity of PVP-stabilized nanostructures is a result of discriminatory binding of analytes within-adsorbed PVP monolayer and a subsequent increase of analyte concentration at the nanostructure surface. Our experimental and theoretical quantum chemical calculations show that BPE binding with PVP-stabilized Au-Ag nanoshells is stronger when the analyte is in its unprotonated form as compared to its cationic, protonated form at a lower pH.