Evaluation of a photodynamic therapy agent using a canine prostate cancer model.

BACKGROUND: Male dogs can develop spontaneous prostate cancer, which is similar physiologically to human disease. Recently, Tweedle and coworkers have developed an orthotopic canine prostate model allowing implanted tumors and therapeutic agents to be tested in a more translational large animal model. We used the canine model to evaluate prostate-specific membrane antigen (PSMA)-targeted gold nanoparticles as a theranostic approach for fluorescence (FL) imaging and photodynamic therapy (PDT) of early stage prostate cancer. METHODS: Dogs (four in total) were immunosuppressed with a cyclosporine-based immunosuppressant regimen and their prostate glands were injected with Ace-1-hPSMA cells using transabdominal ultrasound (US) guidance. Intraprostatic tumors grew in 4-5 weeks and were monitored by ultrasound (US). When tumors reached an appropriate size, dogs were injected intravenously (iv) with PSMA-targeted nano agents (AuNPs-Pc158) and underwent surgery 24 h later to expose the prostate tumors for FL imaging and PDT. Ex vivo FL imaging and histopathological studies were performed to confirm PDT efficacy. RESULTS: All dogs had tumor growth in the prostate gland as revealed by US. Twenty-four hours after injection of PSMA-targeted nano agents (AuNPs-Pc158), the tumors were imaged using a Curadel FL imaging device. While normal prostate tissue had minimal fluorescent signal, the prostate tumors had significantly increased FL. PDT was activated by irradiating specific fluorescent tumor areas with laser light (672 nm). PDT bleached the FL signal, while fluorescent signals from the other unexposed tumor tissues were unaffected. Histological analysis of tumors and adjacent prostate revealed that PDT damaged the irradiated areas to a depth of 1-2 mms with the presence of necrosis, hemorrhage, secondary inflammation, and occasional focal thrombosis. The nonirradiated areas showed no visible damages by PDT. CONCLUSION: We have successfully established a PSMA-expressing canine orthotopic prostate tumor model and used the model to evaluate the PSMA-targeted nano agents (AuNPs-Pc158) in the application of FL imaging and PDT. It was demonstrated that the nano agents allowed visualization of the cancer cells and enabled their destruction when they were irradiated with a specific wavelength of light.

Directional Damping of Plasmons at Metal-Semiconductor Interfaces.

ConspectusOver the past decade, it has been shown that surface plasmons can enhance photoelectric conversion in photovoltaics, photocatalysis, and other optoelectronic applications through their plasmonic absorption and damping processes. However, plasmonically enhanced devices have yet to routinely match or exceed the efficiencies of traditional semiconductor devices. The effect of plasmonic losses dissipates the absorbed photoenergy mostly into heat and that has hampered the realization of superior next-generation plasmonic optoelectronic devices. Several approaches are being explored to alleviate this situation, including using gain to compensate for the plasmonic losses, designing and synthesizing alternative low-loss plasmonic materials, and reducing activation barriers in plasmonic devices and physical thicknesses of photoabsorber layers to lower the plasmonic losses. A newly proposed plasmon-induced interfacial charge-transfer transition (PIICTT) mechanism has proven to be effective in minimizing energy loss during interfacial charge transfer. The PIICTT leads to a damping of metallic plasmonics by directly generating excitons at the plasmonic metal/semiconductor heteronanostructures. This novel concept has been proven to overcome some of the limitations of electron-transfer inefficiencies, renewing a focus on surface plasmon damping processes with the goal that the plasmonic excitation energies of metal nanoparticles can be more efficiently transferred to the adjacent semiconductor components in the absence and presence of an effective interlayer of carrier-selective blocking layer (CSBL). Several theoretical and experimental studies have concluded that efficient plasmon-induced ultrafast hot-carrier transfer was observed in plasmonic-metal/semiconductor heteronanostructures. The PIICTT mechanism may well be a general phenomenon at plasmonic metal/semiconductor, metal/molecule, semiconductor/semiconductor, and semiconductor/molecule heterointerfaces. Thus, the PIICTT presents a new opportunity to limit energy loss in plasmonic-metal nanostructures and increase device efficiencies based on plasmonic coupling. The nonradiative damping of surface plasmons can impact the energy flux direction and thereby provide a new process beyond light trapping, focusing, and hot carrier creation.In this Account, we draw much attention to the benefits of interfacial plasmonic coupling, highlighting recent pioneering discoveries in which plasmon-induced interfacial charge- and energy-transfer processes enable the generation of hot charge carriers near the plasmonic-metal/semiconductor interfaces. This process is likely to increase the photoelectric conversion efficiency, constituting "plasmonic enhancement". We also discuss recent advances in the dynamics of surface plasmon relaxation and highlight exciting new possibilities for plasmonic metals and their interactions with strongly attached semiconductors to provide directional energy fluxes. While this new research area comes on the heels of much elaborate research on both metal and semiconductor nanomaterials, it provides a subtle but important refinement in understanding the optoelectronic properties of materials with far-reaching consequences from fundamental interface science to technological applications. We hope that this Account will contribute to a more systematic description of interface-coupled plasmonics, both fundamentally and in terms of applications toward the design of plasmonic heterostructured devices.

Calculated solvent reorganization entropies, free energies, and fluctuations of the energy gaps for intramolecular electron transfer and excitation of the solvatochromic dye B30.

Intramolecular electron transfer between two biphenyl groups linked by an androstane spacer and excitation of the pyridinium-N-phenolate betaine dye B30 to the first excited singlet state are studied by quantum/classical molecular-dynamics simulations at temperatures between 150 and 300 K in solvents with a range of polarities. Temperature dependences of the solvent reorganization energies, free energies, entropies, and the inhomogeneous broadening of B30's absorption band are examined. The variances of fluctuations of the energy gap between the reactant and product states do not have the direct proportionality to temperature that often is assumed to hold. An explanation for the observations is suggested.

Temperature-dependent solvent reorganization entropies, free energies, and transition dipole strengths for the photoexcitation of Reichardt's dye B30.

Absorption spectra of the solvatochromic dye 2,6-diphenyl-4-2,4,6-triphenyl-1-pyridinophenolate (B30) were measured in seven solvents of varying polarity over temperature ranging from each solvent's freezing point to 300 K. The excitation energies and their variances allowed calculations of the solvent reorganization energies, reorganization free energies and reorganization entropies as functions of temperature. The entropies of solvent packing around the chromophore are found to make major contributions to the reorganization free energies. The variances of the excitation energies depend only weakly on temperature, in disagreement with an expression that is often used for solvent reorganization free energies. Polar solvents reduce the transition dipole strength of B30's long-wavelength absorption band, probably because interactions with the solvent enhance the charge-transfer character of the transition. The dipole strength drops further at low temperatures.

Cu-Sb-S Ternary Semiconductor Nanoparticle Plasmonics.

Semiconductor plasmonics is a recently emerging field that expands the chemical and physical bandwidth of the hitherto well-established noble metallic nanoparticles. Achieving tunable plasmonics from colloidal semiconductor nanocrystals has drawn enormous interest and is promising for plasmon-related applications. However, realizing this goal of tunable semiconductor nanocrystals is currently still a synthetic challenge. Here, we report a colloidal synthesis strategy for highly dispersed, platelet-shaped, antimony-doped copper sulfide semiconductor nanocrystals (Sby-CuxS NCs) with a dominant localized surface plasmon resonance (LSPR) band tunable from the near-infrared into the midvisible spectral range. This work presents the synthesis and quantifies the resulting plasmonic features. It furthermore elucidates the underlying carrier concentration requirements to realize a continuum of LSPR spectra. Building on our previous work on binary plasmonics CuxS, CuxSe, and CuxTe NCs, the present method introduces a much wider and finer tunability with ternary semiconductor plasmonics.

Atomically Dispersed Janus Nickel Sites on Red Phosphorus for Photocatalytic Overall Water Splitting.

Single-atom nickel catalysts hold great promise for photocatalytic water splitting due to their plentiful active sites and cost-effectiveness. Herein, we adopt a reactive-group guided strategy to prepare atomically dispersed nickel catalysts on red phosphorus. The hydrothermal treatment of red phosphorus leads to the formation of P-H and P-OH groups, which behave as the reactive functionalities to generate the dual structure of single-atom P-Ni and P-O-Ni catalytic sites. The produced single-atom sites provide two different functions: P-Ni for water reduction and P-O-Ni for water oxidation. Benefitting from this specific Janus structure, Ni-red phosphorus shows an elevated hydrogen evolution rate compared to Ni nanoparticle-modified red phosphorus under visible-light irradiation. The hydrogen evolution rate was additionally enhanced with increased reaction temperature, reaching 91.51 µmol h-1 at 70 °C, corresponding to an apparent quantum efficiency of 8.9 % at 420 nm excitation wavelength.

Reduction of Electron Repulsion in Highly Covalent Fe-Amido Complexes Counteracts the Impact of a Weak Ligand Field on Excited-State Ordering.

The ability to access panchromatic absorption and long-lived charge-transfer (CT) excited states is critical to the pursuit of abundant-metal molecular photosensitizers. Fe(II) complexes supported by benzannulated diarylamido ligands have been reported to broadly absorb visible light with nanosecond CT excited state lifetimes, but as amido donors exert a weak ligand field, this defies conventional photosensitizer design principles. Here, we report an aerobically stable Fe(II) complex of a phenanthridine/quinoline diarylamido ligand, Fe(ClL)2, with panchromatic absorption and a 3 ns excited-state lifetime. Using X-ray absorption spectroscopy (XAS) and resonant inelastic X-ray scattering (RIXS) at the Fe L-edge and N K-edge, we experimentally validate the strong Fe-Namido orbital mixing in Fe(ClL)2 responsible for the panchromatic absorption and demonstrate a previously unreported competition between ligand-field strength and metal-ligand (Fe-Namido) covalency that stabilizes the 3CT state over the lowest energy triplet metal-centered (3MC) state in the ground-state geometry. Single-crystal X-ray diffraction (XRD) and density functional theory (DFT) suggest that formation of this CT state depopulates an orbital with Fe-Namido antibonding character, causing metal-ligand bonds to contract and accentuating the geometric differences between CT and MC excited states. These effects diminish the driving force for electron transfer to metal-centered excited states and increase the intramolecular reorganization energy, critical properties for extending the lifetime of CT excited states. These findings highlight metal-ligand covalency as a novel design principle for elongating excited state lifetimes in abundant metal photosensitizers.

Targeted Radiosensitizers for MR-Guided Radiation Therapy of Prostate Cancer.

Adjuvant radiotherapy is frequently prescribed to treat cancer. To minimize radiation-related damage to healthy tissue, it requires high precision in tumor localization and radiation dose delivery. This can be achieved by MR guidance and targeted amplification of radiation dose selectively to tumors by using radiosensitizers. Here, we demonstrate prostate cancer-targeted gold nanoparticles (AuNPs) for MR-guided radiotherapy to improve the targeting precision and efficacy. By conjugating Gd(III) complexes and prostate-specific membrane antigen (PSMA) targeting ligands to AuNP surfaces, we found enhanced uptake of AuNPs by PSMA-expressing cancer cells with excellent MR contrast and radiation therapy outcome in vitro and in vivo. The AuNPs binding affinity and r1 relaxivity were dramatically improved and the combination of Au and Gd(III)provided better tumor suppression after radiation. The precise tumor localization by MR and selective tumor targeting of the PSMA-1-targeted AuNPs could enable precise radiotherapy, reduction in irradiating dose, and minimization of healthy tissue damage.

Targeted Gold Nanocluster-Enhanced Radiotherapy of Prostate Cancer.

For over a hundred years, X-rays have been a main component of the radiotherapeutic approaches to treat cancer. Yet, to date, no radiosensitizer has been developed to selectively target prostate cancer. Gold has excellent X-ray absorptivity and is used as a radiotherapy enhancing material. In this work, ultrasmall Au25 nanoclusters (NCs) are developed for selective prostate cancer targeting, radiotherapy enhancement, and rapid clearance from the body. Targeted-Au25 NCs are rapidly and selectively taken up by prostate cancer in vitro and in vivo and also have fast renal clearance. When combined with X-ray irradiation of the targeted cancer tissues, radiotherapy is significantly enhanced. The selective targeting and rapid clearance of the nanoclusters may allow reductions in radiation dose, decreasing exposure to healthy tissue and making them highly attractive for clinical translation.

Visualizing the impact of chloride addition on the microscopic carrier dynamics of MAPbI3 thin films using femtosecond transient absorption microscopy.

The spatial heterogeneity of carrier dynamics in mixed halide perovskite CH3NH3PbI3-xClx thin films with a range of different chloride additions is mapped using femtosecond transient absorption microscopy (TAM). The comparison of TAM images of fibrous and granular polycrystalline CH3NH3PbI3-xClx films indicates that the impact of chloride addition on the local heterogeneity of carrier dynamics is highly dependent on the film preparation method and the resulting morphology. In addition to signals of pristine CH3NH3PbI3, CH3NH3PbI3-xClx films with a fibrous structure show long-lived excited state absorption (ESA) signals in localized, microscopic regions. The ESA signal exhibits transient absorption with a rise time of about 5 ps after the excitation pulse, indicating that these distinct micrograins have preferential carrier trapping properties. The chemical composition of these micrograins does not differ detectably from their surroundings. In contrast, in CH3NH3PbI3-xClx films with a granular structure, Cl addition does not seem to affect the charge carrier dynamics. These results provide insight into the localized effects of halide mixing and on the resulting photophysical properties of mixed halide perovskite materials on the micrometer length scale.

Gold Nanoparticle-Based Fluorescent Theranostics for Real-Time Image-Guided Assessment of DNA Damage and Repair.

Chemotherapeutic dosing, is largely based on the tolerance levels of toxicity today. Molecular imaging strategies can be leveraged to quantify DNA cytotoxicity and thereby serve as a theranostic tool to improve the efficacy of treatments. Methoxyamine-modified cyanine-7 (Cy7MX) is a molecular probe which binds to apurinic/apyrimidinic (AP)-sites, inhibiting DNA-repair mechanisms implicated by cytotoxic chemotherapies. Herein, we loaded (Cy7MX) onto polyethylene glycol-coated gold nanoparticles (AuNP) to selectively and stably deliver the molecular probe intravenously to tumors. We optimized the properties of Cy7MX-loaded AuNPs using optical spectroscopy and tested the delivery mechanism and binding affinity using the DLD1 colon cancer cell line in vitro. A 10:1 ratio of Cy7MX-AuNPs demonstrated a strong AP site-specific binding and the cumulative release profile demonstrated 97% release within 12 min from a polar to a nonpolar environment. We further demonstrated targeted delivery using imaging and biodistribution studies in vivo in an xenografted mouse model. This work lays a foundation for the development of real-time molecular imaging techniques that are poised to yield quantitative measures of the efficacy and temporal profile of cytotoxic chemotherapies.

Optoelectronic Dichotomy of Mixed Halide CH3NH3Pb(Br1- xCl x)3 Single Crystals: Surface versus Bulk Photoluminescence.

In this work, the spatially dependent recombination kinetics of mixed-halide hybrid perovskite CH3NH3Pb(Br1- xCl x)3 (0 ≤ x ≤ 0.19) single crystals are investigated using time-resolved photoluminescence spectroscopy with one- and two-photon femtosecond laser excitation. The introduction of chloride by substituting a fraction of the bromide leads to a decreased lattice constant compared to pure bromide perovskite ( x = 0) and a higher concentration of surface defects. The measured kinetics under one-photon excitation (1PE) shows that increasing the chloride addition quenches the photoluminescence (PL) lifetimes, due to substitution-induced surface defects. In stark contrast, upon 2PE, the PL lifetimes measured deeper in the bulk become longer with increasing chloride addition, until the halide substitution reaches the critical concentration of ∼19%. At x = 19% Cl concentration, a significant reversal of this behavior is observed indicating a change in crystal structure beyond the continuous trends observed at lower percentages of halide substitution ( x ≤ 11%). The observed opposing trends, based on 1PE versus 2PE, highlight a dichotomy between extrinsic (surface) and intrinsic (bulk) effects of chloride substitution on the carrier dynamics in lead bromide perovskites. We discuss the physical relation between halide exchange and bulk carrier lifetimes in CH3NH3PbBr3 in terms of the Rashba effect. We propose that the latter is suppressed at the surface due to disorder in the alignment of the MA and that it increases in the bulk with Cl concentration because of the reduction in lattice parameters, which compresses the space available for the MA orientational degrees of freedom.

Stable 2D Bisthienoacenes: Synthesis, Crystal Packing, and Photophysical Properties.

Two novel 2D bisthienoacenes with annulated thiophene units at different positions were developed. Both 1,2- and 1,4-addition of the α,ß-unsaturated ketone moieties lead to the major formation of four-fold alkylsilylethynyl substituted 2D heteroacenes (namely BTT-4TIPS and BTP-4TIPS). The photophysical, electrochemical properties, crystal packing structures, and charge carrier transport performances were investigated in detail.

Complete Conversion of PbI2 to Methyl Ammonium PbI3 Improves Perovskite Solar Cell Efficiency.

One major disadvantage to the two-step deposition method of perovskite films is the incomplete conversion from PbI2 to perovskite resulting in the presence of a thick PbI2 layer, which hinders charge carrier transportation. In this study, a quaternary ammonium salt has been used to manipulate the crystallization of PbI2 in the first deposition step, which leads to facile incorporation of the methylammonium iodide into the Pb-I lattice and promotes the conversion of PbI2 to perovskite leading to improved device performance.

Nanotechnology for Electroanalytical Biosensors of Reactive Oxygen and Nitrogen Species.

Over the past several decades, nanotechnology has contributed to the progress of biomedicine, biomarker discovery, and the development of highly sensitive electroanalytical / electrochemical biosensors for in vitro and in vivo monitoring, and quantification of oxidative and nitrosative stress markers like reactive oxygen species (ROS) and reactive nitrogen species (RNS). A major source of ROS and RNS is oxidative stress in cells, which can cause many human diseases, including cancer. Therefore, the detection of local concentrations of ROS (e. g. superoxide anion radical; O2•- ) and RNS (e. g. nitric oxide radical; NO• and its metabolites) released from biological systems is increasingly important and needs a sophisticated detection strategy to monitor ROS and RNS in vitro and in vivo. In this review, we discuss the nanomaterials-based ROS and RNS biosensors utilizing electrochemical techniques with emphasis on their biomedical applications.

Electron-transfer dependent photocatalytic hydrogen generation over cross-linked CdSe/TiO2 type-II heterostructure.

Developing type-II heterostructures with a spatial separation of photoexcited electrons and holes is a useful route to promote photocatalytic hydrogen generation. However, few investigations on the charge transfer process across the heterojunction have been carried out, which can allow us to uncover the reaction mechanism. Herein, CdSe quantum dots (QDs) and TiO2 nanocrystals were synthesized and combined in water yielding CdSe/TiO2 type II heterostructures. It was found that mercaptopropionic acid as bifunctional molecules could bind with CdSe and TiO2 to form a cross-linked morphology. The charge carrier dynamics of bare CdSe and CdSe/TiO2 were detected using femtosecond transient absorption spectroscopy. In the presence of TiO2, the average exciton lifetime of CdSe QDs was apparently decreased, owing to the electron transfer from photoexcited CdSe to TiO2. Particularly, the electron-transfer rate from small CdSe QDs (3.0 nm) was much faster than that from big CdSe QDs (4.2 nm). The improved photocatalytic hydrogen generation was observed for CdSe/TiO2 compared to bare CdSe QDs. The enhancement factor for small CdSe QDs was higher than that for big CdSe QDs, which was in good agreement with the electron-transfer rates. This result indicated that the electron transfer between CdSe and TiO2 played an important role in photocatalytic hydrogen generation on CdSe/TiO2 type-II heterostructure. Our study provides a fundamental guidance to construct efficient heterostructured photocatalysts by delicate control of the band alignment.

Imaging the Long Transport Lengths of Photo-generated Carriers in Oriented Perovskite Films.

Organometal halide perovskite has emerged as a promising material for solar cells and optoelectronics. Although the long diffusion length of photogenerated carriers is believed to be a critical factor responsible for the material's high efficiency in solar cells, a direct study of carrier transport over long distances in organometal halide perovskites is still lacking. We fabricated highly oriented crystalline CH3NH3PbI3 (MAPbI3) thin-film lateral transport devices with long channel length (∼120 µm). By performing spatially scanned photocurrent imaging measurements with local illumination, we directly show that the perovskite films prepared here have very long transport lengths for photogenerated carriers, with a minority carrier (electron) diffusion length on the order of 10 µm. Our approach of applying scanning photocurrent microscopy to organometal halide perovskites may be further used to elucidate the carrier transport processes and the vastly different carrier diffusion lengths (∼100 nm to 100 µm) in different types of organometal halide perovskites.

Photoinduced Homolytic Bond Cleavage of the Central Si-C Bond in Porphyrin Macrocycles Is a Charge Polarization Driven Process.

Photoinduced cleavage of the bond between the central Si atom in porphyrin macrocycles and the neighboring carbon atom of an axial alkyl ligand is investigated by both experimental and computational tools. Photolysis and electron paramagnetic resonance measurements indicate that the Si-C bond cleavage of Si-phthalocyanine occurs through a homolytic process. The homolytic process follows a low-lying electronic excitation of about 1.8 eV that destabilizes the carbide bond of similar bond dissociation energy. Using electronic structure calculations, we provide insight into the nature of the excited state and the resulting photocleavage mechanism. We explain this process by finding that the electronic excited state is of a charge transfer character from the axial ligand toward the macrocycle in the reverse direction of the ground state polarization. We find that the homolytic process yielding the radical intermediate is energetically the most stable mechanistic route. Furthermore, we demonstrate using our computational approach that changing the phthalocyanine to smaller ring system enhances the homolytic photocleavage of the Si-C bond by reducing the energetic barrier in the relevant excited states.

Electrophoretic Interpretation of PEGylated NP Structure with and without Peripheral Charge.

Anchoring poly(ethylene glycol) (PEG) to inorganic nanoparticles (NPs) permits control over NP properties for a variety of technological applications. However, the core-shell structure tremendously complicates the interpretation of the ubiquitous ζ-potential, as furnished by electrophoretic light-scattering, capillary electrophoresis or gel electrophoresis. To advance the ζ-potential-and the more fundamental electrophoretic mobility-as a quantitative diagnostic for PEGylated NPs, we synthesized and characterized Au NPs bearing terminally anchored 5 kDa PEG ligands with univalent carboxymethyl end groups. Using the electrophoretic mobilities, acquired over a wide range of ionic strengths, we developed a theoretical model for the distributions of polymer segments, charge, electrostatic potential, and osmotic pressure that envelop the core: knowledge that will help to improve the performance of soft NPs in fundamental research and technological applications.

Femtosecond time-resolved transient absorption spectroscopy of CH3NH3PbI3 perovskite films: evidence for passivation effect of PbI2.

CH3NH3PbI3 perovskite layered films deposited on substrates with and without a titania support structure have been prepared and studied using time-resolved femtosecond transient absorption (fs-TA) spectroscopy in the visible light range (450-800 nm). The electron injection dynamics from the photoexcited perovskite layers to the neighboring film structures could be directly monitored via the transient bleaching dynamics of the perovskite at ∼750 nm and thus systematically studied as a function of the layer-by-layer architecture. In addition, for the first time we could spectrally distinguish transient bleaching at ∼750 nm from laser-induced fluorescence that occurs red-shifted at ∼780 nm. We show that an additional bleach feature at ∼510 nm appears when PbI2 is present in the perovskite film. The amplitudes of the PbI2 and perovskite TA peaks were compared to estimate relative amounts of PbI2 in the samples. Kinetic analysis reveals that perovskite films with less PbI2 show faster relaxation rates than those containing more PbI2. These fast dynamics are attributed to charge carrier trapping at perovskite grain boundaries, and the slower dynamics in samples containing PbI2 are due to a passivation effect, in line with other recently reported work.