RESUMEN
Various conditions in human and veterinary medicine require intestinal resection and anastomosis, and complications from these procedures are frequent. A rapidly collapsible anastomotic guide was developed for small intestinal end-to-end anastomosis and was investigated in order to assess its utility to improve the anastomotic process and to potentially reduce complication rates. A complex manufacturing method for building a polymeric device was established utilizing biocompatible and biodegradable polyvinylpyrrolidone and polyurethane. This combination of polymers would result in rapid collapse of the material. The guide was designed as a hollow cylinder composed of overlaying shingles that separate following exposure to moisture. An in vivo study was performed using commercial pigs, with each pig receiving one standard handsewn anastomosis and one guide-facilitated anastomosis. Pigs were sacrificed after 13 days, at which time burst pressure, maximum luminal diameter, and presence of adhesions were assessed. Burst pressures were not statistically different between treatment groups, but in vivo anastomoses performed with the guide withstood 10% greater luminal burst pressure and maintained 17% larger luminal diameter than those performed using the standard handsewn technique alone. Surgeons commented that the addition of a guide eased the performance of the anastomosis. Hence, a rapidly collapsible anastomotic guide may be beneficial to the performance of intestinal anastomosis.
RESUMEN
Photothermal therapy (PTT) is one of the most promising techniques for cancer tumor ablation. Nanoparticles are increasingly being investigated for use with PTT and can serve as theranostic agents. Based on the ability of near-infrared nano-photo-absorbers to generate heat under laser irradiation, PTT could prove advantageous in certain situations over more classical cancer therapies. To analyze the efficacy of nanoparticle-based PTT, preclinical in vitro studies typically use 2D cultures, but this method cannot completely mimic the complex tumor organization, bioactivity, and physiology that all control the complex penetration depth, biodistribution, and tissue diffusion parameters of nanomaterials in vivo. To fill this knowledge gap, 3D culture systems have been explored for PTT analysis. These models provide more realistic microenvironments that allow spatiotemporal oxygen gradients and cancer cell adaptations to be considered. This review highlights the work that has been done to advance 3D models for cancer microenvironment modeling, specifically in the context of advanced, functionalized nanoparticle-directed PTT.
Asunto(s)
Técnicas de Cultivo de Célula/métodos , Hipertermia Inducida/métodos , Nanoestructuras/uso terapéutico , Fototerapia/métodos , Línea Celular Tumoral , Humanos , Rayos Infrarrojos/uso terapéutico , Rayos Láser , Esferoides Celulares , Nanomedicina Teranóstica/métodos , Microambiente TumoralRESUMEN
Pancreatic cancer is one of the most complex types of cancers to detect, diagnose, and treat. However, the field of nanomedicine has strong potential to address such challenges. When evaluating the diffusion and penetration of theranostic nanoparticles, the extracellular matrix (ECM) is of crucial importance because it acts as a barrier to the tumor microenvironment. In the present study, the penetration of functionalized, fluorescent gold nanorods into large (>500 µm) multicellular 3D tissue spheroids was studied using a multimodal imaging approach. The spheroids were generated by co-culturing pancreatic cancer cells and pancreatic stellate cells in multiple ratios to mimic variable tumor-stromal compositions and to investigate nanoparticle penetration. Fluorescence live imaging, photothermal, and photoacoustic analysis were utilized to examine nanoparticle behavior in the spheroids. Uniquely, the nanorods are intrinsically photoacoustic and photothermal, enabling multi-imaging detection even when fluorescence tracking is not possible or ideal.
Asunto(s)
Imagen Multimodal , Nanopartículas/química , Neoplasias Pancreáticas/diagnóstico por imagen , Células del Estroma/ultraestructura , Línea Celular Tumoral , Colorantes Fluorescentes/química , Colorantes Fluorescentes/farmacología , Oro/química , Humanos , Nanotubos/química , Imagen Óptica , Neoplasias Pancreáticas/patología , Células Estrelladas Pancreáticas/efectos de los fármacos , Células Estrelladas Pancreáticas/ultraestructura , Esferoides Celulares/ultraestructura , Microambiente Tumoral/efectos de los fármacosRESUMEN
Gold nanosystems have been investigated extensively for a variety of applications, from specific cancer cell targeting to tissue regeneration. Specifically, a recent and exciting focus has been the gold nanosystems' interface with neuronal biology. Researchers are investigating the ability to use these systems neuronal applications ranging from the enhancement of stem cell differentiation and therapy to stimulation or inhibition of neuronal activity. Most of these new areas of research are based on the integration of the plasmonic properties of such nanosystems into complex synthetic extracellular matrices (ECM) that can interact and affect positively the activity of neuronal cells. Therefore, the ability to integrate the plasmonic properties of these nanoparticles into multidimensional and morphological structures to support cellular proliferation and activity is potentially of great interest, particularly to address medical conditions that are currently not fully treatable. This review discusses some of the promising developments and unique capabilities offered by the integration of plasmonic nanosystems into morphologically complex ECM devices, designed to control and study the activity of neuronal cells.
RESUMEN
Neurodegenerative diseases and traumatic brain injuries can destroy neurons, resulting in sensory and motor function loss. Transplantation of differentiated neurons from stem cells could help restore such lost functions. Plasmonic gold nanorods (AuNR) were integrated in growth surfaces to stimulate and modulate neural cells in order to tune cell physiology. An AuNR nanocomposite system was fabricated, characterized, and then utilized to study the differentiation of embryonic rat neural stem cells (NSCs). Results demonstrated that this plasmonic surface 1) accelerated differentiation, yielding almost twice as many differentiated neural cells as a traditional NSC culture surface coated with poly-D-lysine and laminin for the same time period; and 2) promoted differentiation of NSCs into neurons and astrocytes in a 2:1 ratio, as evidenced by the expression of relevant marker proteins. These results indicate that the design and properties of this AuNR plasmonic surface would be advantageous for tissue engineering to address neural degeneration.
Asunto(s)
Diferenciación Celular/efectos de los fármacos , Nanotubos/química , Enfermedades Neurodegenerativas/terapia , Neuronas/trasplante , Animales , Astrocitos/trasplante , Lesiones Traumáticas del Encéfalo/patología , Lesiones Traumáticas del Encéfalo/terapia , Células Cultivadas , Células Madre Embrionarias/efectos de los fármacos , Oro/química , Oro/farmacología , Humanos , Células-Madre Neurales/efectos de los fármacos , Células-Madre Neurales/trasplante , Enfermedades Neurodegenerativas/patología , Neuronas/efectos de los fármacos , RatasRESUMEN
Nanoparticles from magnetotactic bacteria have been used in conventional imaging, drug delivery, and magnetic manipulations. Here, we show that these natural nanoparticles and their bioinspired hybrids with near-infrared gold nanorods and folic acid can serve as molecular high-contrast photoacoustic probes for single-cell diagnostics and as photothermal agents for single-cell therapy using laser-induced vapor nanobubbles and magnetic field as significant signal and therapy amplifiers. These theranostics agents enable the detection and photomechanical killing of triple negative breast cancer cells that are resistant to conventional chemotherapy, with just one or a few low-energy laser pulses. In studies in vivo, we discovered that circulating tumor cells labeled with the nanohybrids generate transient ultrasharp photoacoustic resonances directly in the bloodstream as the basis for new super-resolution photoacoustic flow cytometry in vivo. These properties make natural and bioinspired magnetic nanoparticles promising biocompatible, multimodal, high-contrast, and clinically relevant cellular probes for many in vitro and in vivo biomedical applications.
Asunto(s)
Nanopartículas de Magnetita/uso terapéutico , Técnicas Fotoacústicas/métodos , Análisis de la Célula Individual/métodos , Animales , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos/métodos , Oro/uso terapéutico , Humanos , Hipertermia Inducida , Ratones , Nanopartículas/uso terapéutico , Nanotubos , Neoplasias/patología , Fototerapia , Nanomedicina TeranósticaRESUMEN
The use of graphene for biomedical and other applications involving humans is growing and shows practical promise. However, quantifying the graphitic nanomaterials that interact with cells and assessing any corresponding cellular response is extremely challenging. Here, we report an effective approach to quantify graphene interacting with single cells that utilizes combined multimodal-Raman and photoacoustic spectroscopy. This approach correlates the spectroscopic signature of graphene with the measurement of its mass using a quartz crystal microbalance resonator. Using this technique, we demonstrate single cell noninvasive quantification and multidimensional mapping of graphene with a detection limit of as low as 200 femtograms. Our investigation also revealed previously unseen graphene-induced changes in surface receptor expression in dendritic cells of the immune system. This tool integrates high-sensitivity real-time detection and monitoring of nanoscale materials inside single cells with the measurement of induced simultaneous biological cell responses, providing a powerful method to study the impact of nanomaterials on living systems and as a result, the toxicology of nanoscale materials.
Asunto(s)
Grafito/química , Nanoestructuras/química , Receptores de Superficie Celular/metabolismo , Animales , Línea Celular , Humanos , Ratones , Ratones Endogámicos C57BL , Microscopía Fluorescente , Técnicas Fotoacústicas , Tecnicas de Microbalanza del Cristal de Cuarzo , Receptores de Superficie Celular/química , Receptores de Superficie Celular/genética , Espectrometría RamanRESUMEN
The outstanding properties of Teflon AF-2400-chemical, optical, etc-inspired us to make modifications to enhance its hydrophobicity. We prepared an AF-2400/indium tin oxide (ITO) nanocomposite by a spin coating technique at room temperature, using the AF-2400 polymer as the matrix and ITO nanoparticles as the filler. Different ITON concentrations ranging from 3 to 30 mg ml-1 were prepared to study the effect of nanoparticle loading on the films' properties and superhydrophobicity. The effect of spin speed and annealing temperature was also studied. Atomic force microscopy, x-ray photoelectron spectroscopy, and UV-vis analysis were employed to characterize the prepared films. The results indicated that the film's low surface energy and nano/micro-features made it superhydrophobic. Increasing the ITON concentration to 15 mg ml-1 improved the superhydrophobicity of the composite film by increasing the surface roughness. The coating showed superhydrophobic behavior with a static contact angle (SCA) around 152° and contact angle hysteresis less than 2°. The nanocomposite films also exhibited excellent thermal stability, sustaining temperatures as high as 240 °C without losing their superhydrophobic behavior. Three models, Wenzel, Cassie-Baxter, and Shuttleworth-Bailey, were used to predict the SCA. The results confirmed that the latter model gave the best prediction. In addition to superhydrophobicity, the AF-2400/ITON films coated on a glass substrate showed very high transparency-around 95% in the visible and infrared ranges. An effective medium theory, the Bergman representation, was used to simulate the transmittance of the AF-2400/ITON nanocomposites. The measured and simulated transmittance values were in good agreement in the visible range. Based on our results, this coating may be highly useful for many practical applications, including solar cell coatings, chemical resistance protective coatings, and more.
RESUMEN
Carbon-based nanoparticles (CBNs) are nanomaterials that have been shown to be plant growth regulators. Here, we investigated the effects of long-term exposure to multi-walled carbon nanotubes (MWCNTs) on the growth of three important crops (barley, soybean, and corn). The tested species were cultivated in hydroponics supplemented with 50 µg/mL MWCNTs. After 20 weeks of continuous exposure to the nanomaterials, no significant toxic effects on plant development were observed. Several positive phenotypical changes were recorded, in addition to the enhancement of photosynthesis in MWCNT-exposed crops. Raman spectroscopy with point-by-point mapping proved that the MWCNTs in the hydroponic solution moved into all tested species and were distributed in analyzed organs (leaves, stems, roots, and seeds). Our results confirmed the significant potential of CBN in plant agriculture. However, the documented presence of MWCNTs in different organs of all exposed crops highlighted the importance of detailed risk assessment of nanocontaminated plants moving into the food chain.
Asunto(s)
Glycine max/química , Hordeum/química , Nanotubos de Carbono/análisis , Zea mays/química , Productos Agrícolas/química , Productos Agrícolas/crecimiento & desarrollo , Hordeum/crecimiento & desarrollo , Hidroponía , Hojas de la Planta/química , Hojas de la Planta/crecimiento & desarrollo , Raíces de Plantas/química , Raíces de Plantas/crecimiento & desarrollo , Glycine max/crecimiento & desarrollo , Factores de Tiempo , Zea mays/crecimiento & desarrolloRESUMEN
A 2D multifunctional nanocomposite system of gold nanorods (AuNRs) was developed. Gold nanorods were functionalized via polyethylene glycol with a terminal amine, and, were characterized using transmission and scanning electron microscopy, ultra violet-visible and X-ray photoelectron spectroscopy, and Zeta-potential. The system was cytocompatible to and maintained the integrity of Schwann cells. The neurogenic potential of adipose tissue - derived human mesenchymal stem cells (hMSCs) was evaluated in vitro. The expression pattern and localization of Vimentin confirmed the mesenchymal origin of cells and tracked morphological changes during differentiation. The expression patterns of S100ß and glial fibrillary acidic protein (GFAP), were used as indicator for neural differentiation. Results suggested that this process was enhanced when the cells were seeded on the AuNRs compared to the tissue-culture surface. The present study indicates that the design and the surface properties of the AuNRs enhances neural differentiation of hMSCs and hence, would be beneficial for neural tissue engineering scaffolds.
Asunto(s)
Diferenciación Celular , Oro , Células Madre Mesenquimatosas/citología , Nanocompuestos , Nanotubos , Células-Madre Neurales/citología , Línea Celular , Células Cultivadas , Oro/química , Humanos , Células Madre Mesenquimatosas/metabolismo , Mitocondrias/metabolismo , Nanocompuestos/química , Nanocompuestos/ultraestructura , Nanotubos/química , Nanotubos/ultraestructura , Células-Madre Neurales/metabolismo , Neuronas/citología , Neuronas/metabolismo , Células de Schwann/citología , Células de Schwann/metabolismoRESUMEN
Multifunctional nanoparticles have high potential as targeting delivery vehicles for cancer chemotherapy. In this study, silver-decorated gold nanorods (AuNR\Ag) have been successfully used to deliver specific, targeted chemotherapy against breast cancer (MCF7) and prostate carcinoma (PC3) cell lines. Doxorubicin, a commonly used chemotherapy, and anti-Epithelial cell adhesion molecule (anti-EpCAM) antibodies were covalently bonded to thiolated polyethylene glycol-coated AuNR\Ag, and the resultant system was used to deliver the drugs to cancer cells in vitro. Furthermore, these nanoparticles have a unique spectral signature by surface enhanced Raman spectroscopy (SERS), which enables reliable detection and monitoring of the distribution of these chemotherapy constructs inside cells. The development of interest in a plasmonic nano drugs system with unique spectroscopic signatures could result in a clinical approach to the precise targeting and visualization of cells and solid tumors while delivering molecules for the enhanced treatment of cancerous tumors.
Asunto(s)
Antineoplásicos/administración & dosificación , Doxorrubicina/administración & dosificación , Portadores de Fármacos/química , Oro/química , Nanotubos/química , Plata/química , Anticuerpos Monoclonales/administración & dosificación , Antineoplásicos/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Materiales Biocompatibles Revestidos/síntesis química , Materiales Biocompatibles Revestidos/química , Doxorrubicina/farmacología , Molécula de Adhesión Celular Epitelial/inmunología , Humanos , Terapia Molecular Dirigida , Espectrometría RamanRESUMEN
Dendritic cells (DCs) can acquire, process, and present antigens to T-cells to induce an immune response. For this reason, targeting cancer antigens to DCs in order to cause an immune response against cancer is an emerging area of nanomedicine that has the potential to redefine the way certain cancers are treated. The use of plasmonically active silver-coated gold nanorods (henceforth referred to as plasmonic nano vectors (PNVs)) as potential carriers for DC tumor vaccines has not been presented before. Effective carriers must be able to be phagocytized by DCs, present low toxicity, and induce the maturation of DCs-an early indication of an immune response. When we treated DCs with the PNVs, we found that the cell viability of DCs was unaffected, up to 200 µg/ml. Additionally, the PNVs associated with the DCs as they were phagocytized and they were found to reside within intracellular compartments such as endosomes. More importantly, the PNVs were able to induce expression of surface markers indicative of DC activation and maturation, i.e. CD40, CD86, and MHC class II. These results provide the first evidence that PNVs are promising carriers for DC-based vaccines and warrant further investigating for clinical use.
Asunto(s)
Antígeno B7-2/metabolismo , Antígenos CD40/metabolismo , Células Dendríticas/inmunología , Oro/farmacología , Antígenos de Histocompatibilidad Clase II/farmacología , Plata/farmacología , Animales , Diferenciación Celular/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Células Dendríticas/citología , Células Dendríticas/efectos de los fármacos , Nanopartículas del Metal/química , Ratones , Nanotubos/química , FagocitosisRESUMEN
Graphene-based nanomaterials have received significant attention in the last decade due to their interesting properties. Its electrical and thermal conductivity and strength make graphene well suited for a variety of applications, particularly for use as a composite material in plastics. Furthermore, much work is taking place to utilize graphene as a biomaterial for uses such as drug delivery and tissue regeneration scaffolds. Owing to the rapid progress of graphene and its potential in many marketplaces, the potential toxicity of these materials has garnered attention. Graphene, while simple in its purest form, can have many different chemical and physical properties. In this paper, we describe our toxicity evaluation of pristine graphene and a functionalized graphene sample that has been oxidized for enhanced hydrophilicity, which was synthesized from the pristine sample. The samples were characterized by X-ray photoelectron spectroscopy, Raman spectroscopy, infrared spectroscopy, thermogravimetric analysis, zeta-potential, atomic force microscopy and electron microscopy. We discuss the disagreement between the size of imaged samples analyzed by atomic force microscopy and by transmission electron microscopy. Furthermore, the samples each exhibit quite different surface chemistry and structure, which directly affects their interaction with aqueous environments and is important to consider when evaluating the toxicity of materials both in vitro and in vivo. Copyright © 2017 John Wiley & Sons, Ltd.
Asunto(s)
Fulerenos/toxicidad , Grafito/toxicidad , Nanopartículas/toxicidad , Animales , Fulerenos/química , Grafito/química , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Microscopía de Fuerza Atómica , Microscopía Electrónica de Transmisión , Estructura Molecular , Nanopartículas/química , Oxidación-Reducción , Tamaño de la Partícula , Espectroscopía de Fotoelectrones , Medición de Riesgo , Espectroscopía Infrarroja por Transformada de Fourier , Espectrometría Raman , Relación Estructura-Actividad , Propiedades de Superficie , Termogravimetría , Pruebas de ToxicidadRESUMEN
Graphene, a crystalline allotrope or carbon, presents numerous useful properties; however, its toxicity is yet to be determined. One of the most dramatic and irreversible toxic abilities of carbon nanomaterials is the induction of DNA fragmentation produced by endogenous cellular endonucleases. This study demonstrated that pristine graphene exposed to cultured kidney tubular epithelial cells is capable of inducing DNA fragmentation measured by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, which is usually associated with cell death. TUNEL (cell death) and endonuclease activity measured using a near infrared fluorescence probe was significantly higher in cells containing graphene aggregates detected by Raman spectroscopy. The elevation of TUNEL coincided with the increased abundance of heme oxygenase 1 (HO-1), heat shock protein 90 (HSP90), active caspase-3 and endonucleases (deoxyribonuclease I [DNase I] and endonuclease G [EndoG]), as measured by quantitative immunocytochemistry. Specific inhibitors for HO-1, HSP90, caspase-3, DNase I and EndoG almost completely blocked the DNA fragmentation induced by graphene exposure. Therefore, graphene induces cell death through oxidative injury, caspase-mediated and caspase-independent pathways; and endonucleases DNase I and EndoG are important for graphene toxicity. Inhibition of these pathways may ameliorate cell injury produced by graphene. Copyright © 2017 John Wiley & Sons, Ltd.
Asunto(s)
Daño del ADN , Desoxirribonucleasa I/metabolismo , Endodesoxirribonucleasas/metabolismo , Células Epiteliales/efectos de los fármacos , Grafito/toxicidad , Túbulos Renales/efectos de los fármacos , Nanopartículas/toxicidad , Animales , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Línea Celular , Desoxirribonucleasa I/antagonistas & inhibidores , Relación Dosis-Respuesta a Droga , Endodesoxirribonucleasas/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Células Epiteliales/enzimología , Células Epiteliales/patología , Proteínas HSP90 de Choque Térmico/metabolismo , Hemo Oxigenasa (Desciclizante)/antagonistas & inhibidores , Hemo Oxigenasa (Desciclizante)/metabolismo , Túbulos Renales/enzimología , Túbulos Renales/patología , Estrés Oxidativo/efectos de los fármacos , Ratas , Medición de Riesgo , Factores de TiempoRESUMEN
Conventional flow cytometry is a versatile tool for drug research and cell characterization. However, it is poorly suited for quantification of non-fluorescent proteins and artificial nanomaterials without the use of additional labeling. The rapid growth of biomedical applications for small non-fluorescent nanoparticles (NPs) for drug delivery and contrast and therapy enhancement, as well as research focused on natural cell pigments and chromophores, demands high-throughput quantification methods for the non-fluorescent components. In this work, we present a novel photoacoustic (PA) fluorescence flow cytometry (PAFFC) platform that combines NP quantification though PA detection with conventional in vitro flow cytometry sample characterization using fluorescence labeling. PAFFC simplifies high-throughput analysis of cell-NP interactions, optimization of targeted nanodrugs, and NP toxicity assessment, providing a direct correlation between NP uptake and characterization of toxicity markers for every cell.
RESUMEN
Due to the distinctive physical, electrical, and chemical properties of graphene nanomaterials, numerous efforts pursuing graphene-based biomedical and industrial applications are underway. Oxidation of pristine graphene surfaces mitigates its otherwise hydrophobic characteristic thereby improving its biocompatibility and functionality. Yet, the potential widespread use of oxidized graphene derivatives raises concern about adverse impacts on human health. The p53 tumor suppressor protein maintains cellular and genetic stability after toxic exposures. Here, we show that p53 functional status correlates with oxygen functionalized graphene (f-G) cytotoxicity and genotoxicity in vitro. The f-G exposed p53-competent cells, but not p53-deficient cells, initiated G0 /G1 phase cell cycle arrest, suppressed reactive oxygen species, and entered apoptosis. There was p53-dependent f-G genotoxicity evident as increased structural chromosome damage, but not increased gene mutation or chromatin loss. In conclusion, the cytotoxic and genotoxic potential for f-G in exposed cells was dependent on the p53 functional status. These findings have broad implications for the safe and effective implementation of oxidized graphene derivatives into biomedical and industrial applications. Published 2017. This article has been contributed to by US Government employees and their work is in the public domain in the USA.
Asunto(s)
Linfocitos B/efectos de los fármacos , Grafito/toxicidad , Nanopartículas/toxicidad , Proteína p53 Supresora de Tumor/metabolismo , Apoptosis/efectos de los fármacos , Linfocitos B/metabolismo , Linfocitos B/patología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Transformada , Aberraciones Cromosómicas/inducido químicamente , Relación Dosis-Respuesta a Droga , Grafito/química , Humanos , Pérdida de Heterocigocidad , Oxidación-Reducción , Especies Reactivas de Oxígeno/metabolismo , Medición de Riesgo , Factores de Tiempo , Proteína p53 Supresora de Tumor/deficiencia , Proteína p53 Supresora de Tumor/genéticaRESUMEN
Optical techniques, including Raman, photothermal and photoacoustic microscopy and spectroscopy, have been intensively explored for the sensitive and accurate detection of various diseases. Rapid advances in lasers, photodetectors, and nanotechnology have led to the development of Raman spectroscopy, particularly surface-enhanced Raman scattering (SERS), as a promising imaging modality that can help diagnose many diseases. This review focuses on the major recent advances in Raman spectroscopy and SERS-enhancing contrast nanoagents, as well as their potential to transition from a proof-of-concept approach to a cancer detection tool in vitro and in vivo.
Asunto(s)
Nanopartículas , Nanotubos de Carbono , Neoplasias/diagnóstico , Espectrometría Raman/métodos , Animales , Humanos , Resonancia por Plasmón de Superficie/métodosRESUMEN
Raman spectroscopy and surface-enhanced raman scattering (SERS) have the potential to improve the detection and monitoring of various diseases, particularly cancer, with or without the support of multifunctional active nanosystems. This review is focused on the recent advances that have made Raman a major tool for treatment guidance for surgical tumor resection or for analytical monitoring of various therapies, such as photodynamic therapy, photothermal therapy, and drug delivery. The potential of Raman spectroscopy and nanosytems to further improve cancer treatments is also discussed.
Asunto(s)
Nanopartículas , Nanotubos de Carbono , Neoplasias/terapia , Espectrometría Raman/métodos , Animales , Humanos , Neoplasias/diagnóstico , Resonancia por Plasmón de Superficie/métodosRESUMEN
Multicomponent nano-agents were designed and built via a core-shell approach to enhance their surface enhanced Raman scattering (SERS) signals. These nano-agents had 36 nm × 12 nm gold nanorod cores coated by 4 nm thick silver shell films and a subsequent thin bifunctional thiolated polyethylene glycol (HS-PEG-COOH) layer. Ambient time-lapsed SERS signal measurements of these functionalized nanorods taken over a two-week period indicated no signal degradation, suggesting that large portions of the silver shells remained in pure metallic form. The morphology of the nanorods was characterized by transmission electron microscopy (TEM) and ultra-high resolution scanning TEM. X-ray photoelectron spectroscopy (XPS) and Auger electron spectroscopy (AES) were utilized to assess the oxidation states of the silver shells covered by HS-PEG-COOH. The binding energies of Ag 3d XPS spectra yielded very small chemical shifts with oxidation; however, the AES peak shapes gave meaningful information about the extent of oxidation undergone by the nano-agent. While the silver shells without HS-PEG-COOH coatings oxidized significantly, the silver shells with HS-PEG-COOH remained predominantly metallic. In fact, six month-old samples still retained mostly metallic silver shells. These findings further demonstrate the stability and longevity of the nanostructures, indicating their significant potential as plasmonically active agents for highly sensitive detection in various biological systems, including cancer cells, tissues, or even organisms.
RESUMEN
Graphene and its derivative, because of their unique physical, electrical and chemical properties, are an important class of nanomaterials being proposed as foundational materials in nanomedicine as well as for a variety of industrial applications. A major limitation for graphene, when used in biomedical applications, is its poor solubility due to its rather hydrophobic nature. Therefore, chemical functionalities are commonly introduced to alter both its surface chemistry and biochemical activity. Here, we show that surface chemistry plays a major role in the toxicological profile of the graphene structures. To demonstrate this, we chemically increased the oxidation level of the pristine graphene and compared the corresponding toxicological effects along with those for the graphene oxide. X-ray photoelectron spectroscopy revealed that pristine graphene had the lowest amount of surface oxygen, while graphene oxide had the highest at 2.5% and 31%, respectively. Low and high oxygen functionalized graphene samples were found to have 6.6% and 24% surface oxygen, respectively. Our results showed a dose-dependent trend in the cytotoxicity profile, where pristine graphene was the most cytotoxic, with decreasing toxicity observed with increasing oxygen content. Increased surface oxygen also played a role in nanomaterial dispersion in water or cell culture medium over longer periods. It is likely that higher dispersity might result in graphene entering into cells as individual flakes ~1 nm thick rather than as more cytotoxic aggregates. In conclusion, changes in graphene's surface chemistry resulted in altered solubility and toxicity, suggesting that a generalized toxicity profile would be rather misleading. Copyright © 2016 John Wiley & Sons, Ltd.