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1.
Kona ; 37: 224-232, 2020 Jan 10.
Article in English | MEDLINE | ID: mdl-32153313

ABSTRACT

Gold nanoparticles (AuNPs) exhibit unique size-dependent physiochemical properties that make them attractive for a wide range of applications. However, the large-scale availability of precision AuNPs has been minimal. Not only must the required nanoparticles be of precise size and morphology, but they must also be of exceedingly narrow size distribution to yield accurate and reliable performance. The present study aims to synthesize precision AuNPs and to assess the advantages and limitations of the Turkevich method-one of the common chemical synthesis technique. Colloidal AuNPs from 15 nm to 50 nm in diameter were synthesized using the Turkevich method. The effect of the molar ratio of the reagent mixture (trisodium citrate to gold chloride), the scaled-up batch size, the initial gold chloride concentration, and the reaction temperature was studied. The morphology, optical property, surface chemistry, and chemical composition of AuNPs were thoroughly characterized. It was determined that the as-synthesized AuNPs between 15 nm and 30 nm exhibit well-defined size and shape, and narrow size distribution (PDI < 0.20). However, the AuNPs became more polydispersed and less spherical in shape as the particle size increased.

2.
Nano Lett ; 19(2): 793-804, 2019 02 13.
Article in English | MEDLINE | ID: mdl-30616354

ABSTRACT

Understanding the uptake and transport dynamics of engineered nanomaterials (ENMs) by mammalian cells is an important step in designing next-generation drug delivery systems. However, to track these materials and their cellular interactions, current studies often depend on surface-bound fluorescent labels, which have the potential to alter native cellular recognition events. As a result, there is still a need to develop methods capable of monitoring ENM-cell interactions independent of surface modification. Addressing these concerns, here we show how scatter enhanced phase contrast (SEPC) microscopy can be extended to work as a generalized label-free approach for monitoring nanoparticle uptake and transport dynamics. To determine which materials can be studied using SEPC, we turn to Lorenz-Mie theory, which predicts that individual particles down to ∼35 nm can be observed. We confirm this experimentally, demonstrating that SEPC works for a variety of metal and metal oxides, including Au, Ag, TiO2, CeO2, Al2O3, and Fe2O3 nanoparticles. We then demonstrate that SEPC microscopy can be used in a quantitative, time-dependent fashion to discriminate between distinct modes of active cellular transport, including intracellular transport and membrane-assisted transport. Finally, we combine this technique with microcontact printing to normalize transport dynamics across multiple cells, allowing for a careful study of ensemble TiO2 nanoparticle uptake. This revealed three distinct regions of particle transport across the cell, indicating that membrane dynamics play an important role in regulating particle flow. By avoiding fluorescent labels, SEPC allows for a rational exploration of the surface properties of nanomaterials in their native state and their role in endocytosis and cellular transport.


Subject(s)
Microscopy, Phase-Contrast/instrumentation , Nanoparticles/metabolism , Biological Transport , Endocytosis , Equipment Design , Human Umbilical Vein Endothelial Cells , Humans , Metals/analysis , Metals/metabolism , Microscopy, Phase-Contrast/methods , Nanoparticles/analysis , Oxides/analysis , Oxides/metabolism , Surface Properties
3.
J Colloid Interface Sci ; 533: 190-197, 2019 Jan 01.
Article in English | MEDLINE | ID: mdl-30165296

ABSTRACT

Increased reliance on kill based approaches for disinfection raises concerns of antimicrobial resistance development and has significantly elevated the need for alternate approaches for skin and substrate disinfection. This study focuses on reducing harmful microbes from substrates primarily via removal and to a lesser extent by kill. HYPOTHESIS: Functional micro-particles designed to adhere to microbes, with a force greater than the force of microbial adhesion to the substrate, would result in enhanced removal-based disinfection of substrates when subject to an external force. EXPERIMENTS: Silica particles were functionalized with a cationic polymer to bind strongly with bacteria via Coulombic interactions. Disinfection efficacies of substrates with functional particles and control groups were evaluated under conditions relevant for handwashing. FINDINGS: Functionalized silica micro-particles result in ∼4 log reduction of E. coli from an artificial skin substrate in 30 s as compared to a maximum of 1.5 log reduction with control particles. Bacterial viability assays indicate a mechanism of action driven by enhanced removal of bacteria with minimal kill. Particle number density, size and suspension velocity along with strong particle - bacteria interactions have been found to be the primary factors responsible for the enhanced bacterial removal from surfaces.


Subject(s)
Escherichia coli/isolation & purification , Polymers/chemistry , Silicon Dioxide/chemistry , Bacterial Adhesion , Cations/chemistry , Escherichia coli/chemistry , Microbial Viability , Particle Size , Surface Properties
4.
Anal Bioanal Chem ; 410(24): 6141-6154, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29744562

ABSTRACT

Due to the unique physicochemical properties exhibited by materials with nanoscale dimensions, there is currently a continuous increase in the number of engineered nanomaterials (ENMs) used in consumer goods. However, several reports associate ENM exposure to negative health outcomes such as cardiovascular diseases. Therefore, understanding the pathological consequences of ENM exposure represents an important challenge, requiring model systems that can provide mechanistic insights across different levels of ENM-based toxicity. To achieve this, we developed a mussel-inspired 3D microphysiological system (MPS) to measure cardiac contractility in the presence of ENMs. While multiple cardiac MPS have been reported as alternatives to in vivo testing, most systems only partially recapitulate the native extracellular matrix (ECM) structure. Here, we show how adhesive and aligned polydopamine (PDA)/polycaprolactone (PCL) nanofiber can be used to emulate the 3D native ECM environment of the myocardium. Such nanofiber scaffolds can support the formation of anisotropic and contractile muscular tissues. By integrating these fibers in a cardiac MPS, we assessed the effects of TiO2 and Ag nanoparticles on the contractile function of cardiac tissues. We found that these ENMs decrease the contractile function of cardiac tissues through structural damage to tissue architecture. Furthermore, the MPS with embedded sensors herein presents a way to non-invasively monitor the effects of ENM on cardiac tissue contractility at different time points. These results demonstrate the utility of our MPS as an analytical platform for understanding the functional impacts of ENMs while providing a biomimetic microenvironment to in vitro cardiac tissue samples. Graphical Abstract Heart-on-a-chip integrated with mussel-inspired fiber scaffolds for a high-throughput toxicological assessment of engineered nanomaterials.


Subject(s)
Bivalvia , Heart/drug effects , Lab-On-A-Chip Devices , Nanofibers/toxicity , Nanostructures/toxicity , Tissue Scaffolds , Adhesives , Animals , Cells, Cultured , In Vitro Techniques , Indoles/chemistry , Microscopy, Electron, Scanning , Myocytes, Cardiac/cytology , Polyesters/chemistry , Polymers/chemistry , Rats , Rats, Sprague-Dawley , Spectroscopy, Fourier Transform Infrared
5.
Sci Rep ; 8(1): 1894, 2018 01 30.
Article in English | MEDLINE | ID: mdl-29382935

ABSTRACT

Pristine titanium dioxide (TiO2) absorbs ultraviolet light and reflects the entire visible spectrum. This optical response of TiO2 has found widespread application as white pigments in paper, paints, pharmaceuticals, foods and plastic industries; and as a UV absorber in cosmetics and photocatalysis. However, pristine TiO2 is considered to be inert under visible light for these applications. Here we show for the first time that a bacterial contaminant (Staphylococcus aureus-a MRSA surrogate) in contact with TiO2 activates its own photocatalytic degradation under visible light. The present study delineates the critical role of visible light absorption by contaminants and electronic interactions with anatase in photocatalytic degradation using two azo dyes (Mordant Orange and Procion Red) that are highly stable because of their aromaticity. An auxiliary light harvester, polyhydroxy fullerenes, was successfully used to accelerate photocatalytic degradation of contaminants. We designed a contaminant-activated, transparent, photocatalytic coating for common indoor surfaces and conducted a 12-month study that proved the efficacy of the coating in killing bacteria and holding bacterial concentrations generally below the benign threshold. Data collected in parallel with this study showed a substantial reduction in the incidence of infections.

6.
Am J Transl Res ; 9(7): 3293-3303, 2017.
Article in English | MEDLINE | ID: mdl-28804547

ABSTRACT

Lung cancer, primarily non-small cell lung cancer (NSCLC), is the leading cause of cancer mortality and the prognosis of patients with advanced or metastatic NSCLC is poor. Despite significant advances in diagnosis and treatment, little improvement has been seen in NSCLC mortality. Recently, Intratumoral Chemotherapy, a direct local delivery of chemotherapeutic drugs, has shown promise in clinical studies. However, toxicity and high dosage of chemotherapeutic agents used for treatment are a limitation. Moreover, these drugs damage indiscriminately, cancerous as well as normal tissues. Thus, a novel therapeutic strategy that targets only malignant tissue sparing normal tissue becomes an urgent issue. Ephrin receptor-A2 (EphA2), a new biomarker, is over-expressed in NSCLC, but not on normal epithelial cells. Receptor EphA2 is a cell surface protein, which upon binding to its ligand EphrinA1 undergo phosphorylation and degradation which attenuates NSCLC growth. Targeting the tumor, sparing the normal tissue and enhancing the therapeutic effects of ligand proteins are the goal of this project. Thus a novel method, intratumoral EphA2 targeted therapy, has been developed to target the oncogenic receptors on tumor tissue by using albumin mesosphere (AMS) conjugated ephrinA1 in mice bearing NSCLC tumors.

7.
Int J Nanomedicine ; 8: 4481-94, 2013.
Article in English | MEDLINE | ID: mdl-24293999

ABSTRACT

MicroRNAs (miRs) are small noncoding RNA sequences that negatively regulate the expression of target genes by posttranscriptional repression. miRs are dysregulated in various diseases, including cancer. let-7a miR, an antioncogenic miR, is downregulated in lung cancers. Our earlier studies demonstrated that let-7a miR inhibits tumor growth in malignant pleural mesothelioma (MPM) and could be a potential therapeutic against lung cancer. EphA2 (ephrin type-A receptor 2) tyrosine kinase is overexpressed in most cancer cells, including MPM and non-small-cell lung cancer (NSCLC) cells. Ephrin-A1, a specific ligand of the EphA2 receptor, inhibits cell proliferation and migration. In this study, to enhance the delivery of miR, the miRs were encapsulated in the DOTAP (N-[1-(2.3-dioleoyloxy)propyl]-N,N,N-trimethyl ammonium)/Cholesterol/DSPE (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[cyanur(polyethylene glycol)-2000])-PEG (polyethylene glycol)-cyanur liposomal nanoparticles (LNP) and ephrin-A1 was conjugated on the surface of LNP to target receptor EphA2 on lung cancer cells. The LNP with an average diameter of 100 nm showed high stability, low cytotoxicity, and high loading efficiency of precursor let-7a miR and ephrin-A1. The ephrin-A1 conjugated LNP (ephrin-A1-LNP) and let-7a miR encapsulated LNP (miR-LNP) showed improved transfection efficiency against MPM and NSCLC. The effectiveness of targeted delivery of let-7a miR encapsulated ephrin-A1 conjugated LNP (miR-ephrin-A1-LNP) was determined on MPM and NSCLC tumor growth in vitro. miR-ephrin-A1-LNP significantly increased the delivery of let-7a miR in lung cancer cells when compared with free let-7a miR. In addition, the expression of target gene Ras was significantly repressed following miR-ephrin-A1-LNP treatment. Furthermore, the miR-ephrin-A1-LNP complex significantly inhibited MPM and NSCLC proliferation, migration, and tumor growth. Our results demonstrate that the engineered miR-ephrin-A1-LNP complex is an effective carrier for the targeted delivery of small RNA molecules to lung cancer cells. This could be a potential therapeutic approach against tumors overexpressing the EphA2 receptor.


Subject(s)
Antineoplastic Agents/pharmacology , Ephrin-A1/chemistry , Liposomes/pharmacology , Lung Neoplasms , MicroRNAs/pharmacology , Nanoparticles/chemistry , Antineoplastic Agents/chemistry , Carcinoma, Non-Small-Cell Lung , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Drug Delivery Systems/methods , Ephrin-A1/metabolism , Humans , Liposomes/chemistry , MicroRNAs/chemistry , MicroRNAs/genetics , Transfection/methods
8.
J Mater Chem B ; 1(45): 6312-6320, 2013 Dec 07.
Article in English | MEDLINE | ID: mdl-24634776

ABSTRACT

A facile synthesis of 3-6 nm, water dispersible, near-infrared (NIR) emitting, quantum dots (QDs) magnetically doped with Fe is presented. Doping of alloyed CdTeS nanocrystals with Fe was achieved in situ using a simple hydrothermal method. The magnetic quantum dots (MQDs) were capped with NAcetyl-Cysteine (NAC) ligands, containing thiol and carboxylic acid functional groups to provide stable aqueous dispersion. The optical and magnetic properties of the Fe doped MQDs were characterized using several techniques. The synthesized MQDs are tuned to emit in the Vis-NIR (530-738 nm) wavelength regime and have high quantum yields (67.5-10%). NIR emitting (738 nm) MQDs having 5.6 atomic% Fe content exhibited saturation magnetization of 85 emu/gm[Fe] at room temperature. Proton transverse relaxivity of the Fe doped MQDs (738 nm) at 4.7 T was determined to be 3.6 mM-1s-1. The functional evaluation of NIR MQDs has been demonstrated using phantom and in vitro studies. These water dispersible, NIR emitting and MR contrast producing Fe doped CdTeS MQDs, in unagglomerated form, have the potential to act as multimodal contrast agents for tracking live cells.

9.
Small ; 8(18): 2856-68, 2012 Sep 24.
Article in English | MEDLINE | ID: mdl-22744832

ABSTRACT

Clinical applications of the indocyanine green (ICG) dye, the only near infrared (NIR) imaging dye approved by the Food and Drug Administration (FDA) in the USA, are limited due to rapid protein binding, fast clearance, and instability in physiologically relevant conditions. Encapsulating ICG in silica particles can enhance its photostability, minimize photobleaching, increase the signal-to-noise (S/N) ratio and enable in vivo studies. Furthermore, a combined magnetic resonance (MR) and NIR imaging particulate can integrate the advantage of high-resolution 3D anatomical imaging with high-sensitivity deep-tissue in-vivo fluorescent imaging. In this report, a novel synthesis technique that can achieve these goals is presented. A reverse-microemulsion-based synthesis protocol is employed to produce 25 nm ICG-doped silica nanoparticles (NPs). The encapsulation of ICG is achieved by manipulating coulombic attractions with bivalent ions and aminated silanes and carrying out silica synthesis in salt-catalyzed, mildly basic pH conditions using dioctyl sulfosuccinate (AOT)/heptane/water microemulsion system. Furthermore, paramagnetic properties are imparted by chelating paramagnetic Gd to the ICG-doped silica NPs. Aqueous ICG-dye-doped silica NPs show increased photostability (over a week) and minimal photobleaching as compared to the dye alone. The MR and optical imaging capabilities of these particles are demonstrated through phantom, in vitro and in vivo experiments. The described particles have the potential to act as theranostic agents by combining photodynamic therapy through the absorption of NIR irradiated light.


Subject(s)
Gadolinium/chemistry , Indocyanine Green/chemistry , Nanoparticles/chemistry , Silicon Dioxide/chemistry , Cell Line, Tumor , Fluorescent Dyes/chemistry , Humans , Magnetic Resonance Imaging , Optical Imaging , Spectroscopy, Near-Infrared
10.
Int J Nanomedicine ; 7: 2739-50, 2012.
Article in English | MEDLINE | ID: mdl-22701319

ABSTRACT

BACKGROUND: Theranostic nanomaterials composed of fluorescent and photothermal agents can both image and provide a method of disease treatment in clinical oncology. For in vivo use, the near-infrared (NIR) window has been the focus of the majority of studies, because of greater light penetration due to lower absorption and scatter of biological components. Therefore, having both fluorescent and photothermal agents with optical properties in the NIR provides the best chance of improved theranostic capabilities utilizing nanotechnology. METHODS: We developed nonplasmonic multi-dye theranostic silica nanoparticles (MDT-NPs), combining NIR fluorescence visualization and photothermal therapy within a single nanoconstruct comprised of molecular components. A modified NIR fluorescent heptamethine cyanine dye was covalently incorporated into a mesoporous silica matrix and a hydrophobic metallo-naphthalocyanine dye with large molar absorptivity was loaded into the pores of these fluorescent particles. The imaging and therapeutic capabilities of these nanoparticles were demonstrated in vivo using a direct tumor injection model. RESULTS: The fluorescent nanoparticles are bright probes (300-fold enhancement in quantum yield versus free dye) that have a large Stokes shift (>110 nm). Incorporation of the naphthalocyanine dye and exposure to NIR laser excitation results in a temperature increase of the surrounding environment of the MDT-NPs. Tumors injected with these NPs are easily visible with NIR imaging and produce significantly elevated levels of tumor necrosis (95%) upon photothermal ablation compared with controls, as evaluated by bioluminescence and histological analysis. CONCLUSION: MDT-NPs are novel, multifunctional nanomaterials that have optical properties dependent upon the unique incorporation of NIR fluorescent and NIR photothermal dyes within a mesoporous silica platform.


Subject(s)
Fluorescent Dyes/pharmacology , Nanoparticles/chemistry , Neoplasms, Experimental/diagnosis , Neoplasms, Experimental/drug therapy , Spectroscopy, Near-Infrared/methods , Animals , Carbocyanines/chemistry , Cell Line, Tumor , Female , Fluorescent Dyes/chemistry , Histocytochemistry , Mice , Mice, Inbred BALB C , Microscopy, Electron, Scanning , Necrosis , Neoplasms, Experimental/chemistry , Silicon Dioxide/chemistry
11.
Chemosphere ; 89(1): 96-101, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22583785

ABSTRACT

Adsorption of natural organic matter (NOM) on nanoparticles can have dramatic impacts on particle dispersion resulting in altered fate and transport as well as bioavailability and toxicity. In this study, the adsorption of Suwannee River humic acid (SRHA) on silver nanoparticles (nano-Ag) was determined and showed a Langmuir adsorption at pH 7 with an adsorption maximum of 28.6 mg g(-1) nano-Ag. It was also revealed that addition of <10 mg L(-1) total organic carbon (TOC) increased the total Ag content suspended in the aquatic system, likely due to increased dispersion. Total silver content decreased with concentrations of NOM greater than 10mg TOCL(-1) indicating an increase in nanoparticle agglomeration and settling above this concentration. However, SRHA did not have any significant effect on the equilibrium concentration of ionic Ag dissolved in solution. Exposure of Daphnia to nano-Ag particles (50 µg L(-1) and pH 7) produced a linear decrease in toxicity with increasing NOM. These results clearly indicate the importance of water chemistry on the fate and toxicity of nanoparticulates.


Subject(s)
Humic Substances/analysis , Metal Nanoparticles/toxicity , Rivers/chemistry , Silver/chemistry , Water Pollutants, Chemical/toxicity , Adsorption , Animals , Daphnia/drug effects , Hydrogen-Ion Concentration , Metal Nanoparticles/chemistry , Water Pollutants, Chemical/chemistry
12.
Int J Nanomedicine ; 7: 351-7, 2012.
Article in English | MEDLINE | ID: mdl-22287844

ABSTRACT

PURPOSE: Photothermal therapy is an emerging cancer treatment paradigm which involves highly localized heating and killing of tumor cells, due to the presence of nanomaterials that can strongly absorb near-infrared (NIR) light. In addition to having deep penetration depths in tissue, NIR light is innocuous to normal cells. Little is known currently about the fate of nanomaterials post photothermal ablation and the implications thereof. The purpose of this investigation was to define the intratumoral fate of nanoparticles (NPs) after photothermal therapy in vivo and characterize the use of novel multidye theranostic NPs (MDT-NPs) for fractionated photothermal antitumor therapy. METHODS: The photothermal and fluorescent properties of MDT-NPs were first characterized. To investigate the fate of nanomaterials following photothermal ablation in vivo, novel MDT-NPs and a murine mammary tumor model were used. Intratumoral injection of MDT-NPs and real-time fluorescence imaging before and after fractionated photothermal therapy was performed to study the intratumoral fate of MDT-NPs. Gross tumor and histological changes were made comparing MDT-NP treated and control tumor-bearing mice. RESULTS: The dual dye-loaded mesoporous NPs (ie, MDT-NPs; circa 100 nm) retained both their NIR absorbing and NIR fluorescent capabilities after photoactivation. In vivo MDT-NPs remained localized in the intratumoral position after photothermal ablation. With fractionated photothermal therapy, there was significant treatment effect observed macroscopically (P = 0.026) in experimental tumor-bearing mice compared to control treated tumor-bearing mice. CONCLUSION: Fractionated photothermal therapy for cancer represents a new therapeutic paradigm enabled by the application of novel functional nanomaterials. MDT-NPs may advance clinical treatment of cancer by enabling fractionated real-time image guided photothermal therapy.


Subject(s)
Hyperthermia, Induced/methods , Mammary Neoplasms, Animal/therapy , Nanoparticles/administration & dosage , Animals , Cell Line, Tumor , Infrared Rays , Injections, Intralesional , Mammary Neoplasms, Animal/chemistry , Mammary Neoplasms, Animal/pathology , Mice , Mice, Inbred BALB C , Microscopy, Fluorescence , Nanoparticles/analysis , Nanoparticles/chemistry , Random Allocation , Whole Body Imaging
13.
J Biomed Nanotechnol ; 7(5): 724-9, 2011 Oct.
Article in English | MEDLINE | ID: mdl-22195491

ABSTRACT

We report water-in-oil (W/O) microemulsion synthesis of fluorescently bright and paramagnetically strong bimodal chitosan nanoparticles (BCNPs). The W/O microemulsion system provides a confined environment for producing monodispersed BCNPs. Average particle size as estimated by the Transmission Electron Microscopy was 28 nm. The water to surfactant molar ratio of 22 produced small size fairly monodispersed BCNPs. Fluorescein isothiocyanate (FITC, a fluorescent dye) and Gd-DOTA (a paramagnetic Gd ion chelating agent) were covalently attached to chitosan polymer backbone prior to BCNP synthesis. The purpose of the covalent attachment of fluorescent and paramagnetic labels to chitosan is to prevent leakage of these labels from the BCNPs. The BCNPs were cross-linked with tartaric acid using water-soluble carbodiimide coupling chemistry in order to maintain particulate integrity. Zeta potential value of +27.6 mV confirmed positive surface charge of cross-linked BCNPs. Fluorescence excitation and emission spectra of BCNPs were similar to that of bare FITC spectra, showing characteristic 520 nm emission at the 490 excitation. Paramagnetic gadolinium ion (Gd3+) concentration in the BCNPs was determined by inductively coupled plasma (ICP) emission spectroscopy. The longitudinal (T1) and transverse (T2) proton relaxation times were determined as a function of Gd3+ concentration in the BCNPs at 4.7 Tesla. Proton relaxivity (R1 value) of BCNPs was calculated to be 41.1 mM Gd(-1)s(-1). The reported R1 value of Gd-DOTA chelates is however 5.8 mM Gd(-1)s(-1). High proton relaxivity of BCNPs is attributed to hydrated chitosan environment around Gd chelates which additionally contributed to overall water exchange process. To demonstrate in vitro bioimaging capability, J774 macrophage cells were incubated with BCNPs. Confocal images clearly showed BCNP uptake by J774 cells. Internalization of BCNPs was confirmed by co-labeling J774 cells with a red-emitting membrane dye. BCNP green emission was mostly observed from middle of cells and within the red-emitting membrane boundary.


Subject(s)
Chitosan/chemistry , Nanoparticles/chemistry , Animals , Cell Line , Fluorescein-5-isothiocyanate/chemistry , Gadolinium/chemistry , Magnetic Resonance Spectroscopy , Mice , Microscopy, Fluorescence , Nanoparticles/ultrastructure , Spectrometry, Fluorescence
14.
Artif Intell Med ; 53(2): 119-25, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21868208

ABSTRACT

OBJECTIVE: Accurate cell death discrimination is a time consuming and expensive process that can only be performed in biological laboratories. Nevertheless, it is very useful and arises in many biological and medical applications. METHODS AND MATERIAL: Raman spectra are collected for 84 samples of A549 cell line (human lung cancer epithelia cells) that has been exposed to toxins to simulate the necrotic and apoptotic death. The proposed data mining approach for the multiclass cell death discrimination problem uses a multiclass regularized generalized eigenvalue algorithm for classification (multiReGEC), together with a dimensionality reduction algorithm based on spectral clustering. RESULTS: The proposed algorithmic scheme can classify A549 lung cancer cells from three different classes (apoptotic death, necrotic death and control cells) with 97.78%± 0.047 accuracy versus 92.22 ± 0.095 without the proposed feature selection preprocessing. The spectrum areas depicted by the algorithm corresponds to the 〉C O bond from the lipids and the lipid bilayer. This chemical structure undergoes different change of state based on cell death type. Further evidence of the validity of the technique is obtained through the successful classification of 7 cell spectra that undergo hyperthermic treatment. CONCLUSIONS: In this study we propose a fast and automated way of processing Raman spectra for cell death discrimination, using a feature selection algorithm that not only enhances the classification accuracy, but also gives more insight in the undergoing cell death process.


Subject(s)
Algorithms , Cell Death , Neoplasms/pathology , Apoptosis , Gene Expression Profiling/methods , Humans , Lung Neoplasms/pathology , Reproducibility of Results
15.
PLoS One ; 6(5): e19976, 2011.
Article in English | MEDLINE | ID: mdl-21637768

ABSTRACT

Recent toxicological studies on carbon nanomaterials, including fullerenes, have led to concerns about their safety. Functionalized fullerenes, such as polyhydroxy fullerenes (PHF, fullerols, or fullerenols), have attracted particular attention due to their water solubility and toxicity. Here, we report surprisingly beneficial and/or specific effects of PHF on model organisms representing four kingdoms, including the green algae Pseudokirchneriella subcapitata, the plant Arabidopsis thaliana, the fungus Aspergillus niger, and the invertebrate Ceriodaphnia dubia. The results showed that PHF had no acute or chronic negative effects on the freshwater organisms. Conversely, PHF could surprisingly increase the algal culture density over controls at higher concentrations (i.e., 72% increase by 1 and 5 mg/L of PHF) and extend the lifespan and stimulate the reproduction of Daphnia (e.g. about 38% by 20 mg/L of PHF). We also show that at certain PHF concentrations fungal growth can be enhanced and Arabidopsis thaliana seedlings exhibit longer hypocotyls, while other complex physiological processes remain unaffected. These findings may open new research fields in the potential applications of PHF, e.g., in biofuel production and aquaculture. These results will form the basis of further research into the mechanisms of growth stimulation and life extension by PHF.


Subject(s)
Arabidopsis/growth & development , Aspergillus niger/growth & development , Chlorophyta/growth & development , Daphnia/growth & development , Fullerenes/pharmacology , Models, Biological , Animals , Arabidopsis/drug effects , Aspergillus niger/drug effects , Chlorophyta/drug effects , Daphnia/drug effects , Fullerenes/chemistry , Hydrogen-Ion Concentration/drug effects , Hypocotyl/drug effects , Hypocotyl/growth & development , Hypocotyl/radiation effects , Light , Plant Roots/drug effects , Plant Roots/growth & development , Plant Roots/radiation effects , Seedlings/drug effects , Seedlings/growth & development , Seedlings/radiation effects , Time Factors
16.
J Surg Oncol ; 103(4): 317-25, 2011 Mar 15.
Article in English | MEDLINE | ID: mdl-21337565

ABSTRACT

Approaches for breast cancer treatment are invasive, disfiguring, have significant side-effects, and are not always curative. Nanotechnology is an emerging area which is focused on engineering of materials <100 × 10(-9) m. There is significant promise for advancing nanotechnology to improve breast cancer diagnosis and treatment including non-invasive therapy, monitoring response to therapy, advanced imaging, treatment of metastatic disease, and improved nodal staging. Current approaches and important future directions are discussed.


Subject(s)
Breast Neoplasms/diagnosis , Breast Neoplasms/therapy , Nanotechnology , Female , Humans , Nanoparticles
17.
Anal Bioanal Chem ; 399(1): 3-27, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20924568

ABSTRACT

Nanoparticle-based contrast agents are quickly becoming valuable and potentially transformative tools for enhancing medical diagnostics for a wide range of in-vivo imaging modalities. Compared with conventional molecular-scale contrast agents, nanoparticles (NPs) promise improved abilities for in-vivo detection and potentially enhanced targeting efficiencies through longer engineered circulation times, designed clearance pathways, and multimeric binding capacities. However, NP contrast agents are not without issues. Difficulties in minimizing batch-to-batch variations and problems with identifying and characterizing key physicochemical properties that define the in-vivo fate and transport of NPs are significant barriers to the introduction of new NP materials as clinical contrast agents. This manuscript reviews the development and application of nanoparticles and their future potential to advance current and emerging clinical bioimaging techniques. A focus is placed on the application of solid, phase-separated materials, for example metals and metal oxides, and their specific application as contrast agents for in-vivo near-infrared fluorescence (NIRF) imaging, magnetic resonance imaging (MRI), positron emission tomography (PET), computed tomography (CT), ultrasound (US), and photoacoustic imaging (PAI). Clinical and preclinical applications of NPs are identified for a broad spectrum of imaging applications, with commentaries on the future promise of these materials. Emerging technologies, for example multifunctional and theranostic NPs, and their potential for clinical advances are also discussed.


Subject(s)
Contrast Media , Diagnostic Imaging/instrumentation , Nanoparticles , Animals , Contrast Media/chemistry , Diagnostic Imaging/methods , Humans , Nanoparticles/chemistry , Nanotechnology/instrumentation , Nanotechnology/methods
18.
Luminescence ; 26(6): 390-6, 2011.
Article in English | MEDLINE | ID: mdl-20960573

ABSTRACT

UNLABELLED: Optical imaging is a cornerstone of modern oncologic research. The aim of this study is to determine the value of a new tool to enhance bioluminescent and fluorescent sensitivity for facilitating very-low-level signal detection in vivo. EXPERIMENTAL: For bioluminescent imaging experiments, a luciferase expressing breast cancer cell line with metastatic phenotype was implanted orthotopically into the mammary fat pad of mice. For fluorescent imaging experiments, near-infrared (NIR) nanoparticles were injected intratumorally and subcutaneously into mice. Images were compared in mice with and without application of the 'Gator' Mouse Suit (GMS). RESULTS: The GMS was associated with early detection and quantification of metastatic bioluminescent very-low-level signal not possible with conventional imaging strategies. Similarly, NIR nanoparticles that were undetectable in locations beyond the primary injection site could be visualized and their very-low-level signal quantifiable with the aid of the GMS. CONCLUSION: The GMS is a device which has tremendous potential for facilitating the development of bioluminescent models and fluorescent nanomaterials for translational oncologic applications.


Subject(s)
Breast Neoplasms/diagnosis , Nanoparticles , Neoplasm Metastasis/diagnosis , Animals , Breast Neoplasms/pathology , Cell Line, Tumor , Disease Models, Animal , Female , Humans , Luminescence , Mice , Neoplasm Transplantation
19.
Langmuir ; 26(20): 15837-44, 2010 Oct 19.
Article in English | MEDLINE | ID: mdl-20839856

ABSTRACT

Copper species coated silica nanoparticles (CuOXS) were synthesized for odor removal application. Coating with copper increased the capacity of silica nanoparticles for eliminating a model odor-ethyl mercaptan. Surface area, pore size distribution, and electron paramagnetic resonance spectroscopy analyses indicated that, at lower copper concentrations, copper species preferentially adsorb in 20 Å pores of silica. These copper species in a dispersed state are effective in catalytic removal of ethyl mercaptan. The best performance of copper-coated silica nanoparticles was achieved at a copper concentration of 3 wt %, at which all 20 Å nanopores were filled with isolated copper species. At higher copper loading, copper species are present as clusters on silica surfaces, which were found to be less effective in removing ethyl mercaptan. Gas chromatography experiments were carried out to verify catalytic conversion of ethyl mercaptan to diethyl disulfide by CuOXS particles. The present study suggests that the nature of the copper species and their site of adsorption, as well as state of dispersion, are important parameters to be considered for catalytic removal of sulfur-containing compounds. These parameters are critical for designing high-performance catalytic copper-coated silica nanoparticles for applications such as deodorization, removal of sulfur compounds from crude oil, hydrogenation, and antimicrobial activity.

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