A Real-Time Surface Enhanced Raman Spectroscopy Study of Plasmonic Photothermal Cell Death Using Targeted Gold Nanoparticles

Plasmonic nanoparticles are increasingly utilized in biomedical applications including imaging, diagnostics, drug delivery, and plasmonic photothermal therapy (PPT). PPT involves the rapid conversion of light into heat by plasmonic nanoparticles targeted to a tumor, causing hyperthermia-induced cell death. These nanoparticles can be passively targeted utilizing the enhanced permeability and retention effect, or actively targeted using proteins, peptides, or other small molecules. Here, we report the use of actively targeted spherical gold nanoparticles (AuNPs), both to induce PPT cell death, and to monitor the associated molecular changes through time-dependent surface enhanced Raman spectroscopy within a single cell. We monitored these changes in real-time and found that heat generated from the aggregated nanoparticles absorbing near-infrared (NIR) laser light of sufficient powers caused modifications in the protein and lipid structures within the cell and ultimately led to cell death. The same molecular changes were observed using different nanoparticle sizes and laser intensities, indicating the consistency of the molecular changes throughout PPT-induced cell death from actively targeted AuNPs. We also confirmed these observations by comparing them to reference spectra obtained by cell death induced by oven heating at 100 °C. The ability to monitor PPT-induced cell death in real-time will help understand the changes on a molecular level and offers us a basis to understand the molecular mechanisms involved in photothermal cancer cell death

Electrochemical Synthesis of Ammonia from N₂ and H₂O under Ambient Conditions Using Pore-Size-Controlled Hollow Gold Nanocatalysts with Tunable Plasmonic Properties

An electrochemical nitrogen reduction reaction (NRR) could provide an alternative pathway to the Haber–Bosch process for clean, sustainable, and decentralized NH3 production when it is coupled with renewably derived electricity sources. Developing an electrocatalyst that overcomes sluggish kinetics due to the challenges associated with N2 adsorption and cleavage and that also produces NH3 with a reasonable yield and efficiency is an urgent need. Here, we engineer the size and density of pores in the walls of hollow Au nanocages (AuHNCs) by tuning their peak localized surface plasmon resonance (LSPR); in this way, we aim to enhance the rate of electroreduction of N2 to NH3. The interdependency between the pore size/density, the peak LSPR position, the silver content in the cavity, and the total surface area of the nanoparticle should be realized for further optimization of hollow plasmonic nanocatalysts in electrochemical NRRs

Rapid Thermal Tuning of Chromophore Structure in Membrane Protein

We show that the configuration and the optical property of the retinal chromophore in bacteriorhodopsin (bR) can be tuned dynamically from the all-trans configuration to the 13-cis by using a nanosecond laser-induced temperature-jump. The rapid bleach in the visible absorption optical density of retinal has an apparent formation time of ca. 170 ns, whereas the relaxation process finishes within tens of ms. The dynamical transition of retinal from the all-trans to 13-cis species is believed to occur as a result of rapid protein conformational change especially in the vicinity of retinal binding site. Our study reveals the intrinsic dynamical aspect of the retinal chromophore with respect to the protein structure

Surface Plasmon Coupling and Its Universal Size Scaling in Metal Nanostructures of Complex Geometry: Elongated Particle Pairs and Nanosphere Trimers

Recently, we showed that the plasmon resonance coupling between two interacting metal nanoparticles decays with the interparticle separation (in units of particle size) with the same universal trend independent of particle size or shape, metal type, or medium. This universal scaling behavior has been shown to apply to lithographically fabricated nanoparticle pairs, the metal nanoshell, plasmonic dielectric sensors, and the plasmon ruler useful in determining intersite distances in biological systems. In this article, we use electrodynamic simulations to examine the general applicability of this universal scaling behavior to more complex nanostructure geometries, for example, head-to-tail dimers of elongated particles of different aspect ratios and curvatures and a trimer of nanospheres. We find that the plasmon coupling between two elongated nanoparticles interacting head-to-tail decays according to the same universal law if the interparticle separation is scaled by the particle long-axis dimension. The absolute plasmon coupling strength, however, depends on the particle shape (i.e., aspect ratio and curvature), without affecting the universal scaling behavior. We also show that universal scaling is valid in a system of three interacting nanospheres, a first step toward extending this model to chains/arrays/assemblies of metal nanoparticles

Changing Catalytic Activity during Colloidal Platinum Nanocatalysis Due to Shape Changes: Electron-Transfer Reaction

The shape distribution of the catalytic nanoparticles and the activation energy of the electron-transfer reaction between hexacyanoferrate (III) and thiosulfate ions were determined at different times during the course of the reaction. The activation energy is found to increase during the reaction when dominantly tetrahedral nanoparticles are used, decreases slightly when dominantly cubic nanoparticles are used, and remains almost unchanged when spherical nanoparticles are used. Corresponding changes in the shape of the tetrahedral and cubic, but not spherical, shape is observed. This is consistent with the changes in the activation energy that are observed. The shape distribution and activation energy of dominantly spherical nanoparticles is found to remain stable during the course of the reaction

Gold Nanoframes: Very High Surface Plasmon Fields and Excellent Near-Infrared Sensors

The sensing efficiency or factor of noble metal nanoparticles is defined as the wavelength shift of the surface plasmon resonance extinction peak position per unit change in the refractive index of the surrounding medium. The sensitivity of different shapes and sizes of gold nanoparticles has been studied by many investigators and found to depend on the plasmon field strength. As a result, the sensitivity factors were found to be larger for hollow nanoparticles than for solid ones of comparable dimensions. This is due to the strong plasmonic fields resulting from the coupling between the external and internal surface plasmon fields in the hollow nanoparticles. In the present paper, the sensitivity factors of a large number of gold nanoframes of different size and wall thickness have been determined by experimental and theoretical computation (using the discrete dipole approximation method). The dependence of the sensitivity factors and the plasmon field strength on the wall thickness and the size of the nanoframes has been determined and is discussed. The sensitivity factors are found to increase linearly with the aspect ratio (wall length/wall thickness) of the nanoframes and are especially sensitive to a decrease in the wall thickness. In comparison with other plasmonic nanoparticles, it is found that nanoframes have sensitivity factors that are 12, 7, and 3 times higher than those of gold nanospheres, gold nanocubes, and gold nanorods, respectively, as well as more than several hundred units higher than those of comparable-size gold nanocages

Universal Scaling of Plasmon Coupling in Metal Nanostructures: Extension from Particle Pairs to Nanoshells

It has been recently shown that the strength of plasmon coupling between a pair of plasmonic metal nanoparticles falls as a function of the interparticle gap scaled by the particle size with a near-exponential decay trend that is universally independent of nanoparticle size, shape, metal type, or medium dielectric constant. In this letter, we extend this universal scaling behavior to the dielectric core−metal shell nanostructure. By using extended Mie theory simulations of silica core−metal nanoshells, we show that when the shift of the nanoshell plasmon resonance wavelength scaled by the solid nanosphere resonance wavelength is plotted against the shell thickness scaled by the core radius, nanoshells with different dimensions (radii) exhibit the same near-exponential decay. Thus, the nanoshell system becomes physically analogous to the particle-pair system, i.e., the nanoshell plasmon resonance results from the coupling of the inner shell surface (cavity) and the outer shell surface (sphere) plasmons over a separation distance essentially given by the metal shell thickness, which is consistent with the plasmon hybridization model of Prodan, Halas, and Nordlander. By using the universal scaling behavior in the nanoshell system, we propose a simple expression for predicting the dipolar plasmon resonance of a silica−gold nanoshell of given dimensions

Surface Plasmon Resonance Sensitivity of Metal Nanostructures: Physical Basis and Universal Scaling in Metal Nanoshells

In this letter, we show using extended Mie theory simulations that the sensitivity of the surface plasmon resonance (SPR) of a dielectric core-metal nanoshell increases near-exponentially as the ratio of the shell thickness-to-core radius is decreased. The plasmon sensitivity thus shows the same universal scaling behavior established recently for plasmon coupling in metal nanoshells and that in metal nanoparticle pairs. From these observations, we propose that the sensitivity is determined by the ease of surface polarization of the electrons in the nanostructure by the light. This can be used as a generalized physical principle for designing plasmonic nanostructures for effective SPR chemical and biological sensing

Detecting and Destroying Cancer Cells in More than One Way with Noble Metals and Different Confinement Properties on the Nanoscale

Today, 1 in 2 males and 1 in 3 females in the United States will develop cancer at some point during their lifetimes, and 1 in 4 males and 1 in 5 females in the United States will die from the disease. New methods for detection and treatment have dramatically improved cancer care in the United States. However, as improved detection and increasing exposure to carcinogens has led to higher rates of cancer incidence, clinicians and researchers have not balanced that increase with a similar decrease in cancer mortality rates. This mismatch highlights a clear and urgent need for increasingly potent and selective methods with which to detect and treat cancers at their earliest stages.Nanotechnology, the use of materials with structural features ranging from 1 to 100 nm in size, has dramatically altered the design, use, and delivery of cancer diagnostic and therapeutic agents. The unique and newly discovered properties of these structures can enhance the specificities with which biomedical agents are delivered, complementing their efficacy or diminishing unintended side effects. Gold (and silver) nanotechnologies afford a particularly <i>unique</i> set of physiological and optical properties which can be leveraged in applications ranging from in vitro/vivo therapeutics and drug delivery to imaging and diagnostics, surgical guidance, and treatment monitoring.Nanoscale diagnostic and therapeutic agents have been in use since the development of micellar nanocarriers and polymer–drug nanoconjugates in the mid-1950s, liposomes by Bangham and Watkins in the mid-1960s, and the introduction of polymeric nanoparticles by Langer and Folkman in 1976. Since then, nanoscale constructs such as dendrimers, protein nanoconjugates, and inorganic nanoparticles have been developed for the systemic delivery of agents to specific disease sites. Today, more than 20 FDA-approved diagnostic or therapeutic nanotechnologies are in clinical use with roughly 250 others in clinical development. The global market for nano-enabled medical technologies is expected to grow to $70–160 billion by 2015, rivaling the current market share of biologics worldwide.In this Account, we explore the emerging applications of noble metal nanotechnologies in cancer diagnostics and therapeutics carried out by our group and by others. Many of the novel biomedical properties associated with gold and silver nanoparticles arise from confinement effects: (i) the confinement of photons within the particle which can lead to dramatic electromagnetic scattering and absorption (useful in sensing and heating applications, respectively); (ii) the confinement of molecules around the nanoparticle (useful in drug delivery); and (iii) the cellular/subcellular confinement of particles within malignant cells (such as selective, nuclear-targeted cytotoxic DNA damage by gold nanoparticles). We then describe how these confinement effects relate to specific aspects of diagnosis and treatment such as (i) laser photothermal therapy, optical scattering microscopy, and spectroscopic detection, (ii) drug targeting and delivery, and (iii) the ability of these structures to act as intrinsic therapeutic agents which can selectively perturb/inhibit cellular functions such as division. We intend to provide the reader with a unique physical and chemical perspective on both the design and application of these technologies in cancer diagnostics and therapeutics. We also suggest a framework for approaching future research in the field