Growth Dynamics of Colloidal Silver-Gold Core-Shell Nanoparticles Studied by In Situ Second Harmonic Generation and Extinction Spectroscopy.

The in situ growth dynamics of colloidal silver-gold core-shell (Ag@Au CS) nanoparticles (NPs) in water are monitored in a stepwise synthesis approach using time-dependent second harmonic generation (SHG) and extinction spectroscopy. Three sequential additions of chloroauric acid, sodium citrate, and hydroquinone are added to the silver nanoparticle solution to grow a gold shell around a silver core. The first addition produces a stable urchin-like surface morphology, while the second and third additions continue to grow the gold shell thickness as the surface becomes more smooth and uniform, as determined using transmission electron microscopy. The extinction spectra after each addition are compared to finite-difference time-domain (FDTD) calculations, showing large deviations for the first and second additions due to the bumpy surface morphology and plasmonic hotspots while showing general agreement after the third addition reaches equilibrium. The in situ SHG signal is dominated by the NP surface, providing complementary information on the growth time scales due to changes to the surface morphology. This combined approach of synthesis and characterization of Ag@Au CS nanoparticles with in situ SHG spectroscopy, extinction spectroscopy, and FDTD calculations provides a detailed foundation for investigating complex colloidal nanoparticle growth mechanisms and dynamics in developing enhanced plasmonic nanomaterial technologies.

Influence of Temperature on Molecular Adsorption and Transport at Liposome Surfaces Studied by Molecular Dynamics Simulations and Second Harmonic Generation Spectroscopy.

A fundamental understanding of the kinetics and thermodynamics of chemical interactions at the phospholipid bilayer interface is crucial for developing potential drug-delivery applications. Here we use molecular dynamics (MD) simulations and surface-sensitive second harmonic generation (SHG) spectroscopy to study the molecular adsorption and transport of a small organic cation, malachite green (MG), at the surface of 1,2-dioleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DOPG) liposomes in water at different temperatures. The temperature-dependent adsorption isotherms, obtained by SHG measurements, provide information on adsorbate concentration, free energy of adsorption, and associated changes in enthalpy and entropy, showing that the adsorption process is exothermic, resulting in increased overall entropy. Additionally, the molecular transport kinetics are found to be more rapid under higher temperatures. Corresponding MD simulations are used to calculate the free energy profiles of the adsorption and the molecular orientation distributions of MG at different temperatures, showing excellent agreement with the experimental results.

Monitoring the growth dynamics of colloidal gold-silver core-shell nanoparticles using in situ second harmonic generation and extinction spectroscopy.

The growth dynamics of gold-silver core-shell (Au@Ag) nanoparticles are studied using in situ time-dependent second harmonic generation (SHG) and extinction spectroscopy to investigate the nanoparticle shell formation. The silver shell is grown by reduction of silver cations onto a 14 nm gold core using ascorbic acid in colloidal aqueous solution under varying reaction concentrations producing Au@Ag nanoparticles of final sizes ranging from 51 to 78 nm in diameter. The in situ extinction spectra show a rapid increase in intensity on the timescale of 5-6 s with blue shifting and narrowing of the plasmonic peak during the silver shell formation. The in situ SHG signals show an abrupt rise at early times of the reaction, followed by a time-dependent biexponential decrease, where the faster SHG lifetime corresponds to the timescale of the shell growth, and where the slower SHG lifetime is attributed to changes in the nanoparticle surface charge density. A large enhancement in the SHG signal at early stages of the reaction is caused by plasmonic hot spots due to the nanoparticle surface morphology, which becomes smoother as the reaction proceeds. The final extinction spectra are compared to finite-difference time-domain (FDTD) calculations, showing general agreement with experiment, where the plasmon peak red shifts and increases in spectral width as the silver shell thickness increases. These in situ SHG and extinction spectroscopy results, combined with FDTD calculations, help characterize the complicated processes involved in colloidal nanoparticle shell formation in real time for developing potential plasmon-enhanced nanomaterial applications.

Combinatorial Delivery of miRNA-Nanoparticle Conjugates in Human Adipose Stem Cells for Amplified Osteogenesis.

It is becoming more apparent in tissue engineering applications that fine temporal control of multiple therapeutics is desirable to modulate progenitor cell fate and function. Herein, the independent temporal control of the co-delivery of miR-148b and miR-21 mimic plasmonic nanoparticle conjugates to induce osteogenic differentiation of human adipose stem cells (hASCs), in a de novo fashion, is described. By applying a thermally labile retro-Diels-Alder caging and linkage chemistry, these miRNAs can be triggered to de-cage serially with discrete control of activation times. The method relies on illumination of the nanoparticles at their resonant wavelengths to generate sufficient local heating and trigger the untethering of the Diels-Alder cycloadduct. Characterization of the photothermal release using fluorophore-tagged miRNA mimics in vitro is carried out with fluorescence measurements, second harmonic generation, and confocal imaging. Osteogenesis of hASCs from the sequential co-delivery of miR-21 and miR-148b mimics is assessed using xylenol orange and alizarin red staining of deposited minerals, and quantitative polymerase chain reaction for gene expression of osteogenic markers. The results demonstrate that sequential miRNA mimic activation results in upregulation of osteogenic markers and mineralization relative to miR-148b alone, and co-activation of miR-148b and miR-21 at the same time.

Molecular Adsorption and Transport at Liposome Surfaces Studied by Molecular Dynamics Simulations and Second Harmonic Generation Spectroscopy.

A fundamental understanding of the factors that determine the interactions with and transport of small molecules through phospholipid membranes is crucial in developing liposome-based drug delivery systems. Here we combine time-dependent second harmonic generation (SHG) measurements with molecular dynamics simulations to elucidate the events associated with adsorption and transport of the small molecular cation, malachite green isothiocyanate (MGITC), in colloidal liposomes of different compositions. The molecular transport of MGITC through the liposome bilayer is found to be more rapid in 1,2-dioleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) and 1,2-dioleoyl-sn-glycero-3-phospho-l-serine (DOPG and DOPS, respectively) liposomes, while the molecular transport is slower in 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) liposomes. Interestingly, MGITC is observed to neither adsorb nor transport in trimethyl quinone-1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (QPADOPE) liposomes due to shielding by the quinone group. The modified Langmuir adsorption isotherm model is used to determine the free energy of adsorption for MGITC, which is found to be less negative in DOPC than in DOPG and DOPS, caused by lower electrostatic interactions between the positively charged dye and the zwitterionic DOPC liposome surface. The results are compared to our previous investigations, which showed that malachite green (MG) adsorbs and transports in DOPG and DOPS liposomes but not in DOPC and QPADOPE liposomes. Molecular dynamics simulations are used to investigate the adsorption and transport properties of MG and MGITC in DOPC and DOPG liposomes using umbrella sampling to determine the free energy profiles and interfacial molecular orientations. Together, these time-resolved SHG studies and corresponding molecular dynamics simulations characterize the complicated chemical interactions at different lipid membranes to provide key molecular-level insights for potential drug delivery applications. The results also point toward understanding the role of chemical functional groups, in this case isothiocyanate, in controlling molecular adsorption at and transport through lipid bilayers.

Near-Infrared Photothermal Release of siRNA from the Surface of Colloidal Gold-Silver-Gold Core-Shell-Shell Nanoparticles Studied with Second-Harmonic Generation.

Photothermal release of oligonucleotides from the surface of plasmonic nanoparticles represents a promising platform for spatiotemporal controlled drug delivery. Here we demonstrate the use of novel gold-silver-gold core-shell-shell (CSS) nanoparticles to study the photothermal cleaving and release of micro-RNA (miRNA) mimics or small interfering RNA (siRNA) under nearinfrared (NIR) irradiation. The furan-maleimide-based Diels-Alder adduct cleaves thermally above 60 °C and is used to bind siRNA to the colloidal nanoparticle surface in water. We investigate the photothermal cleaving kinetics of siRNA under different NIR laser powers using surface-sensitive time-dependent second-harmonic generation (SHG) spectroscopy. The photothermal release of siRNA from the surface of CSS nanoparticles is significantly higher than that from the surface of gold nanoparticles (GNPs) under similar experimental conditions. These results demonstrate that plasmonic CSS nanoparticles with photothermal cleaving linkers have important potential applications for nanoparticle-based NIR-mediated drug-delivery systems.

Resonance Energies and Lifetimes from the Analytic Continuation of the Coupling Constant Method: Robust Algorithms and a Critical Analysis.

The energy of a metastable state can be computed by adding an artificial stabilizing potential to the Hamiltonian, increasing the stabilization until the metastable state is turned into a bound one, and then further increasing the stabilization until enough bound-state data have been collected so that these can be extrapolated back to vanishing stabilization. The lifetime of the metastable state can be obtained from the same data, but only if the extrapolation is performed by analytic continuation. This extrapolation method is called analytic continuation of the coupling constant (ACCC). Here we introduce preconditioning schemes for two of the three established extrapolation algorithms and critically compare results from all three extrapolation schemes in a variety of situations: As examples for resonance states serve the π* temporary anions of ethylene and formaldehyde as well as a model potential, which provides a case where input data with full numeric precision are available. In the data collection step, three different stabilizing potentials are employed, a Coulomb potential, a short-range Coulomb potential, and a soft-box Voronoi potential. Effects of different orders of the extrapolating Padé approximant are investigated, and last, the energy range of input data for the extrapolation is studied. Moreover, all ACCC results are compared to resonance parameters that have been independently obtained with the same theoretical method, but with a different continuum approach-complex scaling for the model and complex absorbing potentials for the temporary anions.