131 research outputs found
Raman and Computational Study on the Adsorption of Xanthine on Silver Nanocolloids
Xanthine is a nucleobase, deriving from adenine and guanine by deamination and oxidation processes, which may deposit in the human body causing diseases, similar to uric acid. Here, we have investigated the adsorption of xanthine on silver colloidal nanoparticles by means of surface-enhanced Raman scattering (SERS) with an exciting radiation in the near-infrared spectral region, where interference due to fluorescence does not occur, along with density functional theory calculations of molecule/metal model systems. By adopting a combined experimental and computational approach, we have identified the "marker" SERS bands of xanthine and the tautomer that preferentially binds the silver particles, as well as the molecular group involved in the interaction with metal. This investigation allows using the FT-SERS spectroscopy for biosensory and diagnostic purposes in body fluids, detecting abnormal levels of xanthine, and preventing metabolic diseases
In Vitro Examinations of Cell Death Induction and the Immune Phenotype of Cancer Cells Following Radiative-Based Hyperthermia with 915 MHz in Combination with Radiotherapy
Multimodal tumor treatment settings consisting of radiotherapy and immunomodulating agents such as immune checkpoint inhibitors are more and more commonly applied in clinics. In this context, the immune phenotype of tumor cells has a major influence on the anti-tumor immune response as well as the composition of the tumor microenvironment. A promising approach to further boost anti-tumor immune responses is to add hyperthermia (HT), i.e., heating the tumor tissue between 39 °C to 45 °C for 60 min. One key technique is the use of radiative hyperthermia systems. However, knowledge is limited as to how the frequency of the used radiative systems affects the immune phenotype of the treated tumor cells. By using our self-designed in vitro hyperthermia system, we compared cell death induction and expression of immune checkpoint molecules (ICM) on the tumor cell surface of murine B16 melanoma and human MDA-MB-231 and MCF-7 breast cancer cells following HT treatment with clinically relevant microwaves at 915 MHz or 2.45 GHz alone, radiotherapy (RT; 2 × 5 Gy or 5 × 2 Gy) alone or in combination (RHT). At 44 °C, HT alone was the dominant cell death inductor with inactivation rates of around 70% for B16, 45% for MDA-MB-231 and 35% for MCF-7 at 915 MHz and 80%, 60% and 50% at 2.45 GHz, respectively. Additional RT resulted in 5-15% higher levels of dead cells. The expression of ICM on tumor cells showed time-, treatment-, cell line- and frequency-dependent effects and was highest for RHT. Computer simulations of an exemplary spherical cell revealed frequency-dependent local energy absorption. The frequency of hyperthermia systems is a newly identified parameter that could also affect the immune phenotype of tumor cells and consequently the immunogenicity of tumors
Tumor Cell-Based Vaccine Generated With High Hydrostatic Pressure Synergizes With Radiotherapy by Generating a Favorable Anti-tumor Immune Microenvironment
Dendritic cell (DC)-based vaccines pulsed with high hydrostatic pressure (HHP)-inactivated tumor cells have been demonstrated to be a promising immunotherapy for solid tumors. We focused on sole injection of tumor cells that were inactivated by HHP and their combination with local radiotherapy (RTx) for in vivo induction of anti-tumor immune responses. HHP-treatment of tumor cells resulted in pre-dominantly necrotic cells with degraded DNA. We confirmed that treatments at 200 MPa or higher completely inhibited the formation of tumor cell colonies in vitro. No tumor growth was seen in vivo after injection of HHP-treated tumor cells. Single vaccination with HHP-killed tumor cells combined with local RTx significantly retarded tumor growth and improved the survival as shown in B16-F10 and CT26 tumor models. In B16-F10 tumors that were irradiated with 2 × 5Gy and vaccinated once with HHP-killed tumor cells, the amount of natural killer (NK) cells, monocytes/macrophages, CD4+ T cells and NKT cells was significantly increased, while the amount of B cells was significantly decreased. In both models, a trend of increased CD8+ T cell infiltration was observed. Generally, in irradiated tumors high amounts of CD4+ and CD8+ T cells expressing PD-1 were found. We conclude that HHP generates inactivated tumor cells that can be used as a tumor vaccine. Moreover, we show for the first time that tumor cell-based vaccine acts synergistically with RTx to significantly retard tumor growth by generating a favorable anti-tumor immune microenvironment
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Differences of the immune phenotype of breast cancer cells after ex vivo hyperthermia by warm-water or microwave radiation in a closed-loop system alone or in combination with radiotherapy
The treatment of breast cancer by radiotherapy can be complemented by hyperthermia. Little is known about how the immune phenotype of tumor cells is changed thereby, also in terms of a dependence on the heating method. We developed a sterile closed-loop system, using either a warm-water bath or a microwave at 2.45 GHz to examine the impact of ex vivo hyperthermia on cell death, the release of HSP70, and the expression of immune checkpoint molecules (ICMs) on MCF-7 and MDA-MB-231 breast cancer cells by multicolor flow cytometry and ELISA. Heating was performed between 39 and 44◦C. Numerical process simulations identified temperature distributions. Additionally, irradiation with 2 × 5 Gy or 5 × 2 Gy was applied. We observed a release of HSP70 after hyperthermia at all examined temperatures and independently of the heating method, but microwave heating was more effective in cell killing, and microwave heating with and without radiotherapy increased subsequent HSP70 concentrations. Adding hyperthermia to radiotherapy, dynamically or individually, affected the expression of the ICM PD-L1, PD-L2, HVEM, ICOS-L, CD137-L, OX40-L, CD27-L, and EGFR on breast cancer cells. Well-characterized pre-clinical heating systems are mandatory to screen the immune phenotype of tumor cells in clinically relevant settings to define immune matrices for therapy adaption. © 2020 by the authors. Licensee MDPI, Basel, Switzerland
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Plasmonic hot electron transport drives nano-localized chemistry
Nanoscale localization of electromagnetic fields near metallic nanostructures underpins the fundamentals and applications of plasmonics. The unavoidable energy loss from plasmon decay, initially seen as a detriment, has now expanded the scope of plasmonic applications to exploit the generated hot carriers. However, quantitative understanding of the spatial localization of these hot carriers, akin to electromagnetic near-field maps, has been elusive. Here we spatially map hot-electron-driven reduction chemistry with 15 nm resolution as a function of time and electromagnetic field polarization for different plasmonic nanostructures. We combine experiments employing a six-electron photo-recycling process that modify the terminal group of a self-assembled monolayer on plasmonic silver nanoantennas, with theoretical predictions from first-principles calculations of non-equilibrium hot-carrier transport in these systems. The resulting localization of reactive regions, determined by hot-carrier transport from high-field regions, paves the way for improving efficiency in hot-carrier extraction science and nanoscale regio-selective surface chemistry
Near-field interactions between metal nanoparticle surface plasmons and molecular excitons in thin-films: part I: absorption
In this and the following paper (parts I and II, respectively), we systematically study the interactions between surface plasmons of metal nanoparticles (NPs) with excitons in thin-films of organic media. In an effort to exclusively probe near-field interactions, we utilize spherical Ag NPs in a size-regime where far-field light scattering is negligibly small compared to absorption. In part I, we discuss the effect of the presence of these Ag NPs on the absorption of the embedding medium by means of experiment, numerical simulations, and analytical calculations, all shown to be in good agreement. We observe absorption enhancement in the embedding medium due to the Ag NPs with a strong dependence on the medium permittivity, the spectral position relative to the surface plasmon resonance frequency, and the thickness of the organic layer. By introducing a low index spacer layer between the NPs and the organic medium, this absorption enhancement is experimentally confirmed to be a near field effect In part II, we probe the impact of the Ag NPs on the emission of organic molecules by time-resolved and steady-state photoluminescence measurements
Intracellular SERS nanoprobes for distinction of different neuronal cell types.
Distinction between closely related and morphologically similar cells is difficult by conventional methods especially without labeling. Using nuclear-targeted gold nanoparticles (AuNPs) as intracellular probes we demonstrate the ability to distinguish between progenitor and differentiated cell types in a human neuroblastoma cell line using surface-enhanced Raman spectroscopy (SERS). SERS spectra from the whole cell area as well as only the nucleus were analyzed using principal component analysis that allowed unambiguous distinction of the different cell types. SERS spectra from the nuclear region showed the developments during cellular differentiation by identifying an increase in DNA/RNA ratio and proteins transcribed. Our approach using nuclear-targeted AuNPs and SERS imaging provides label-free and noninvasive characterization that can play a vital role in identifying cell types in biomedical stem cell research
Present and Future of Surface-Enhanced Raman Scattering.
The discovery of the enhancement of Raman scattering by molecules adsorbed on nanostructured metal surfaces is a landmark in the history of spectroscopic and analytical techniques. Significant experimental and theoretical effort has been directed toward understanding the surface-enhanced Raman scattering (SERS) effect and demonstrating its potential in various types of ultrasensitive sensing applications in a wide variety of fields. In the 45 years since its discovery, SERS has blossomed into a rich area of research and technology, but additional efforts are still needed before it can be routinely used analytically and in commercial products. In this Review, prominent authors from around the world joined together to summarize the state of the art in understanding and using SERS and to predict what can be expected in the near future in terms of research, applications, and technological development. This Review is dedicated to SERS pioneer and our coauthor, the late Prof. Richard Van Duyne, whom we lost during the preparation of this article
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