Christopher G. Khoury

In vivo particle tracking and photothermal ablation using plasmon-resonant gold nanostars.

UNLABELLED Gold nanostars offer unique plasmon properties that efficiently transduce photon energy into heat for photothermal therapy. Nanostars, with their small core size and multiple long thin branches, exhibit high absorption cross-sections that are tunable in the near-infrared region with relatively low scattering effect, making them efficient photothermal transducers. Here, we demonstrate particle tracking and photothermal ablation both in vitro and in vivo. Using SKBR3 breast cancer cells incubated with bare nanostars, we observed photothermal ablation within 5 minutes of irradiation (980-nm continuous-wave laser, 15 W/cm2). On a mouse injected systemically with PEGylated nanostars for 2 days, extravasation of nanostars was observed and localized photothermal ablation was demonstrated on a dorsal window chamber within 10 minutes of irradiation (785-nm continuous-wave laser, 1.1 W/cm2). These preliminary results of plasmon-enhanced localized hyperthermia are encouraging and have illustrated the potential of gold nanostars as efficient photothermal agents in cancer therapy. FROM THE CLINICAL EDITOR Gold nanostars are tunable in the near-infrared region with low scattering, thus enable photothermal therapy. Encouraging preliminary results of plasmon-enhanced localized hyperthermia both in vitro and in vivo demonstrate that Au nanostars may be efficient photothermal agents for cancer therapy.

Plasmonic nanoprobes: from chemical sensing to medical diagnostics and therapy

This article provides an overview of the development and applications of plasmonics-active nanoprobes in our laboratory for chemical sensing, medical diagnostics and therapy. Molecular Sentinel nanoprobes provide a unique tool for DNA/RNA biomarker detection both in a homogeneous solution or on a chip platform for medical diagnostics. The possibility of combining spectral selectivity and high sensitivity of the surface-enhanced Raman scattering (SERS) process with the inherent molecular specificity of nanoprobes provides an important multiplex diagnostic modality. Gold nanostars can provide an excellent multi-modality platform, combining two-photon luminescence with photothermal therapy as well as Raman imaging with photodynamic therapy. Several examples of optical detection using SERS and photonics-based treatments are presented to illustrate the usefulness and potential of the plasmonic nanoprobes for theranostics, which seamlessly combines diagnostics and therapy.

Plasmonics of 3-D Nanoshell Dimers Using Multipole Expansion and Finite Element Method

The spatial and spectral responses of the plasmonic fields induced in the gap of 3-D nanoshell dimers of gold and silver are comprehensively investigated and compared via theory and simulation using the multipole expansion (ME) and the finite element method (FEM) in COMSOL, respectively. The E-field in the dimer gap was evaluated and compared as a function of shell thickness, interparticle distance, and size. The E-field increased with decreasing shell thickness, decreasing interparticle distance, and increasing size, with the error between the two methods ranging from 1 to 10%, depending on the specific combination of these three variables. This error increases several fold with increasing dimer size, as the quasi-static approximation breaks down. A consistent overestimation of the plasmons fwhm and red shifting of the plasmon peak occurs with FEM, relative to ME, and it increases with decreasing shell thickness and interparticle distance. The size effect that arises from surface scattering of electrons is addressed and shown to be especially prominent for thin shells, for which significant damping, broadening, and shifting of the plasmon band is observed; the size effect also affects large nanoshell dimers, depending on their relative shell thickness, but to a lesser extent. This study demonstrates that COMSOL is a promising simulation environment to quantitatively investigate nanoscale electromagnetics for the modeling and designing of surface-enhanced Raman scattering (SERS) substrates.

Demonstration of surface-enhanced Raman scattering by tunable, plasmonic gallium nanoparticles

Size-controlled gallium nanoparticles deposited on sapphire were explored as alternative substrates to enhance Raman spectral signatures. Galliums resilience following oxidation is inherently advantageous in comparison with silver for practical ex vacuo nonsolution applications. Ga nanoparticles were grown using a simple molecular beam epitaxy-based fabrication protocol, and monitoring their corresponding surface plasmon resonance energy through in situ spectroscopic ellipsometry allowed the nanoparticles to be easily controlled for size. The Raman spectra obtained from cresyl fast violet (CFV) deposited on substrates with differing mean nanoparticle sizes represent the first demonstration of enhanced Raman signals from reproducibly tunable self-assembled Ga nanoparticles. Nonoptimized aggregate enhancement factors of approximately 80 were observed from the substrate with the smallest Ga nanoparticles for CFV dye solutions down to a dilution of 10 ppm.

Investigating the plasmonics of a dipole-excited silver nanoshell: Mie theory versus finite element method

This report compares COMSOLs finite element method (FEM) algorithm with the Mie theory for solving the electromagnetic fields in the vicinity of a silica-silver core-shell nanoparticle when excited by a radiating dipole. The novelty of this investigation lies in the excitation source of the nanoshell system: an oscillating electric dipole is frequently used as a model for both molecular scattering and molecular fluorescence; moreover, a common classical model of atomic or molecular spontaneous emission is a decaying electric dipole. The radiated power spectra were evaluated both analytically and numerically by integrating the Poynting vector around 20, 60 and 100 nm nanoshells, thereby solving the total and scattered fields generated by a dipole positioned inside the core and in the surrounding air medium, respectively. The agreement was excellent in amplitude, plasmon resonance peak position and full width at half-maximum. The FEM algorithm also generates accurate solutions of the near-field electromagnetics in the spatial domain, where the E-field behavior as a function of polar angle theta for a fixed observation radius was evaluated. The quasistatic approximation, which is valid for small nanoparticles, is also employed to assess its limitations relative to the Mie and FEM algorithms.

Plasmonic Gold Nanostars: A Potential Agent for Molecular Imaging and Cancer Therapy

Gold nanostars, with tunable plasmon in the near infrared tissue optic window, generate intense two-photon photoluminescence capable of in vitro cell labeling and in vivo particle tracking. Efficient photothermal ablation therapy is also demonstrated.

Tracking SERS-active nanoprobe intracellular uptake for chemical and biological sensing

A critical aspect of the use of nanoprobes for intracellular studies in chemical and biological sensing involves a fundamental understanding of their uptake and trajectory in cells. In this study, we describe experiments using surface-enhanced Raman scattering (SERS) spectroscopy and mapping to track cellular uptake of plasmonics-active labeled nanoparticles. Three different Raman-active labels with positive, negative, and neutral charges were conjugated to silver colloidal nanoparticles with the aim of spatially and temporally profiling intracellular delivery and tracking of nanoprobes during uptake in single mammalian cells. 1-D Raman spectra and 2-D Raman mapping are used to identify and locate the probes via their SERS signal intensities. Because Raman spectroscopy is very specific for identification of chemical and molecular signatures, the development of functionalized plasmonics-active nanoprobes capable of exploring intracellular spaces and processes has the ability to provide specific information on the effects of biological and chemical pollutants in the intracellular environment. The results indicate that this technique will allow study of when, where, and how these substances affect cells and living organisms.

Reversible Gating of Plasmonic Coupling for Optical Signal Amplification

Amplification of optical signals is useful for a wide variety of applications, ranging from data signal transmission to chemical sensing and biomedical diagnostics. One such application in chemical sensing is surface-enhanced Raman scattering (SERS), an important technique for increasing the Raman signal using the plasmonic effect of enhanced electromagnetic fields associated with metallic nanostructures. One of the most important limitations of SERS-based amplification is the difficulty to reproducibly control the SERS signal. Here, we describe the design and implementation of a unique hybrid system capable of producing reversible gating of plasmonic coupling for Raman signal amplification. The hybrid system is composed of two subsystems: (1) colloidal magneto-plasmonic nanoparticles for SERS enhancement and (2) a micromagnet substrate with an externally applied magnetic field to modulate the colloidal nanoparticles. For this proof of concept demonstration, the nanoparticles were labeled with a Raman-active dye, and it was shown that the detected SERS signal could be reproducibly modulated by controlling the externally applied magnetic field. The developed system provides a simple, robust, inexpensive, and reusable device for SERS signal modulation. These properties will open up new possibilities for optical signal amplification and gating as well for high-throughput, reproducible SERS detection.

Abstract 1966: Plasmonic gold nanostars: A potential agent for molecular imaging and cancer therapy

Gold nanoparticles offer great potential for bioapplication due to their biocompatibility, chemical stability, and plasmon tunability. Due to the increased demand in custom-designed bioapplication, tailoring nanoparticle9s plasmon for a specific application remains an active area of research. Plasmonic gold nanostars, with their sharp tips and small cores, yield unique optical properties in the near infrared region favorable for biological applications. We present a high-yield biocompatible synthesis of gold nanostars, whose geometry is adjustable such that the plasmon band can be tuned into the near-infrared “tissue diagnostic window”. Nanostars offer several interesting plasmon properties including intense surface-enhanced Raman scattering (SERS) for ultrasensitive detection, strong two-photon photoluminescence (TPL) for real-time particle tracking, and efficient photothermal transduction for hyperthermic therapy. Here, we demonstrate nanostars tracking and photothermal ablation both in vitro and in vivo. Using SKBR3 breast cancer cells incubated with bare nanostars, photothermal ablation was observed within 5 minutes of irradiation (980 nm CW laser, 15 W/cm2). On a mouse preinfused systemically with PEGylated nanostars for 2 days, extravasation of nanostars was observed and localized photothermal ablation was demonstrated on a dorsal window chamber within 10 minutes of irradiation (785 nm CW laser, 1.1 W/cm2). These preliminary results have illustrated the theranostic potential of gold nanostars for the use in molecular imaging and cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1966. doi:1538-7445.AM2012-1966