Search

Colloidal crystallization using DNA provides a robust method for fabricating highly programmable nanoparticle superstructures with collective plasmonic properties. Here, we report on the DNA-guided fabrication of 3D plasmonic aggregates from polydisperse gold nanoprisms. We first construct 1D crystals via DNA-induced and shape-directed face-to-face assembly of anisotropic gold nanoprisms. Using the near-Tm thermal annealing approach that promotes long-range DNA-induced interaction and ordering, we then assemble 1D nanoprism crystals into a 3D nanoprism aggregate that exhibits a polycrystalline morphology with nanoscale ordering and microscale dimensions. The presence of closely packed nanoprism arrays over a large area gives rise to strong near-field plasmonic coupling and generates a high density of plasmonic hot spots within the 3D nanoprism aggregates that exhibit excellent surface-enhanced Raman scattering performance. The plasmonic 3D nanoprism aggregates demonstrate significant SERS enhancement (

Purpose Posterior ocular trauma and the subsequent fibrotic retinal complication termed proliferative vitreoretinopathy (PVR) are leading causes of blindness in children and young adults. A previous study suggested that changes occurring within the first month post-trauma can lead to development of PVR later. The aim of this study was to examine the effect of dasatinib, a tyrosine kinase inhibitor clinically used to treat chronic myeloid leukemia, on fibrotic changes occurring within the first month following ocular trauma. Methods A previously established swine ocular trauma model that mimics both contusion and penetrating injuries was used. Dasatinib was administered on days 4 and 18 post-trauma via intravitreal injection of either bolus solution or suspension of a sustained release system incorporated in biodegradable poly (lactic-co-glycolic acid) (PLGA) nanoparticles. Animals were followed up to day 32, and the development of traction full-thickness fold in the posterior retina was assessed. Results A full-thickness retinal fold extending from the wound site developed in 3 out of 4 control eyes injected with PLGA nanoparticles alone at 1 month. Administration of dasatinib solution had little preventative effect with 6 out of 7 eyes developing a fold. In contrast, dasatinib-incorporated PLGA nanoparticle injection significantly reduced the incidence of fold to 1 out of 10 eyes. Conclusions Injection of dasatinib-incorporated PLGA significantly reduced early fibrotic retinal changes which eventually lead to PVR following posterior ocular trauma. Thus, our sustained dasatinib release system can potentially be used to both prevent and/or broaden the surgical treatment window for PVR.

The probability of human exposure to damaging radiation is increased in activities associated with long-term space flight, medical radiation therapies, and responses to nuclear accidents. However, the development of responsive countermeasures to combat radiation damage to biological tissue is lagging behind rates of human exposure. Herein, we report a radiation-responsive drug delivery system that releases doses of curcumin from a chitosan polymer/film in response to low level gamma radiation exposure. As a fibrous chitosan–curcumin polymer, 1 Gy gamma irradiation (137Cs) released 5 ± 1% of conjugated curcumin, while 6 Gy exposure releases 98 ± 1% of conjugated curcumin. The same polymer was formed into a film through solvent casting. The films showed similar, albeit attenuated behavior in water (100% released) and isopropyl alcohol (32% released) with statistically significant drug release following 2 Gy irradiation. ATR FT-IR studies confirmed glycosidic bond cleavage in the chitosan–curcumin polymer in response to gamma radiation exposure. Similar behavior was noted upon exposure of the polymer to 20 cGy (1 GeV amu−1, at 20 cGy min−1) high linear energy transfer (LET) 56Fe radiation based on FTIR studies. Density Functional Theory calculations indicate homolytic bond scission as the primary mechanism for polymer disintegration upon radiation exposure. Films did not change in thickness during the course of radiation exposure. The successful demonstration of radiation-triggered drug release may lead to new classes of radio-protective platforms for developing countermeasures to biological damage from ionizing radiation.

Physical and chemical properties of a redox protein adsorbed to different interfaces of a multilayer immunoassay assembly were studied using a single-mode, electro-active, integrated optical waveguide (SM-EA-IOW) platform. For each interface of the immunoassay assembly (indium tin oxide, 3-aminopropyl triethoxysilane, recombinant protein G, antibody, and bovine serum albumin) the surface density, the adsorption kinetics, and the electron-transfer rate of bound species of the redox-active cytochrome c (Cyt-C) protein were accurately quantified at very low surface concentrations of redox species (from 0.4 to 4% of a full monolayer) using a highly sensitive optical impedance spectroscopy (OIS) technique based on measurements obtained with the SM-EA-IOW platform. The technique is shown here to provide quantitative insights into an important immunoassay assembly for characterization and understanding of the mechanisms of electron transfer rate, the affinity strength of molecular binding, and the associated bio-selectivity. Such methodology and acquired knowledge are crucial for the development of novel and advanced immuno-biosensors.

The utilization of nanoparticle-polymer bead hybrid nanostructures as a SERS substrate depends on the control of the deposition, density, and distribution of nanoparticles on the bead surface. Here we demonstrate the fabrication of a large area SERS substate via a two- step DNA mediated assembly of gold nanoprisms and polystyrene (PS) beads into a large ensemble of beads that are densely coated with nanoprisms. First, nanoprisms are loaded on PS beads through DNA hybridization. The close packed arrangement of anisotropic nanoprisms in different orientations on a bead surface results in a plasmonic substrate with a variable nanogap size ranging 1–20 nm. Nanoprisms-coated beads are then assembled into a large stack or aggregate of beads using a DNA-induced crystallization approach. Each aggregate consists of 20–50 nanoprisms-coated beads, leading to the formation a large area of three-dimensional SERS substrate with a high-density of hot spots for SERS enhancement. An excellent enhancement factor (EF) of 1.09 × 10 5 and a very high detection sensitivity (up to 10–10 M) are observed for the analysis of a probe molecule (Methylene blue) using the SERS substrate.

Janus particles, which possess asymmetric structures and/or multiple surface chemistries, have attracted intense interest due to their capability of multiple distinct interactions with their environment. Most Janus particles synthesis techniques rely on applying coating molecules on isotropic particles. Herein, we demonstrate a method to controllably functionalize both major facets of geometrically anisotropic triangular gold nanoprisms in the size range of 100–200 nm with two distinct molecular coatings (hexadecane thiol or thiolated poly (ethylene) glycol and thiol-modified oligonucleotide), giving rise to the formation of Janus gold nanoprisms. Janus particles orient themselves on the interface of water-chloroform mixture and exhibit variable interaction with both hydrophilic and hydrophobic surfaces due to their amphiphilicity and undergo asymmetric self-assembly behavior with other nanoparticles.

Background AS1411 is a 26-mer G-rich DNA oligonucleotide that forms a variety of G-quadruplex structures. It was identified based on its cancer-selective antiproliferative activity and subsequently determined to be an aptamer to nucleolin, a multifunctional protein that preferentially binds quadruplex nucleic acids and which is present at high levels on the surface of cancer cells. AS1411 has exceptionally efficient cellular internalization compared to non-quadruplex DNA sequences. Scope of review Recent developments related to AS1411 will be examined, with a focus on its use for targeted delivery of therapeutic and imaging agents. Major conclusions Numerous research groups have used AS1411 as a targeting agent to deliver nanoparticles, oligonucleotides, and small molecules into cancer cells. Studies in animal models have demonstrated that AS1411-linked materials can accumulate selectively in tumors following systemic administration. The mechanism underlying the cancer-targeting ability of AS1411 is not completely understood, but recent studies suggest a model that involves: (1) initial uptake by macropinocytosis, a form of endocytosis prevalent in cancer cells; (2) stimulation of macropinocytosis by a nucleolin-dependent mechanism resulting in further uptake; and (3) disruption of nucleolin-mediated trafficking and efflux leading to cargoes becoming trapped inside cancer cells. Significance Human trials have indicated that AS1411 is safe and can induce durable remissions in a few patients, but new strategies are needed to maximize its clinical impact. A better understanding of the mechanisms by which AS1411 targets and kills cancer cells may hasten the development of promising technologies using AS1411-linked nanoparticles or conjugates for cancer-targeted therapy and imaging. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio.

The field of immunosensors, in which an affinity ligand-based immunochemical reaction is coupled to a highly responsive transducer, is growing rapidly. In this chapter we describe the development of two novel photonic strategies for label-free human viral pathogen immunosensing. Two electrically-modulated photonic technologies, named single-mode electro-active integrated optical waveguide (SM-EA-IOW) and electrochemical surface plasmon resonance (EC-SPR) have been developed for specific immunosensing detection. Both sensing photonic strategies are based on incorporating a sandwich immunoassay onto the surfaces of the electro-active photonic devices. To do so, the electro-active photonic platforms are mounted in a micro-electrochemical flow cell where it is functionalized with a monoclonal antibody aimed at a specific target pathogen antigen. Once the target is bound to the device surface, it promotes the capturing of a secondary polyclonal antibody conjugated with a redox-active methylene blue (MB) dye. The methylene blue displays a reversible change in optical absorption throughout a reduction–oxidation transition, which provides an optical signal that can be driven electrically and interrogated with high sensitivity by spectroelectrochemical responses. As a proof of principle, the strategy was applied for the detection of hemagglutinin (HA) protein from the H5N1 avian influenza A virus onto two electro-active photonic devices, the SM-EA-IOW and EC-SPR platforms. The experimental results of the electro-active based immunosensors showed a remarkable limit of detection, ensuring a promising future for these emerging technologies. Their experimental benefits and their intrinsic trade-offs are discussed here.

We show that low temperature processing (100–400 °C) of gold nanoplates (GNPs) permanently shifts their resonant wavelength peak from the infrared to visible (860–650 nm) after an hour at 350 °C. The mechanism is melting-induced shape change; as sharp triangular corners become round the smaller effective GNP diameter produces shorter resonant wavelengths. These wavelength shifts are relevant to GNP-driven microelectromechanical systems, where temperatures of 150–350 °C arise during thin film processing. Strategies to accommodate the observed thermal shifts include starting with particles that have a longer resonant wavelength, ensuring that nanoplates are well-dispersed, and using sub-200 °C processing methods.

// Mohammad T. Malik 1, 5 , Martin G. O’Toole 2 , Lavona K. Casson 1, 5 , Shelia D. Thomas 1, 5 , Gina T. Bardi 1, 5 , Elsa Merit Reyes-Reyes 1, 5 , Chin K. Ng 3 , Kyung A. Kang 4 , Paula J. Bates 1, 5 1 Departments of Medicine, University of Louisville, Louisville, Kentucky, USA 2 Departments of Bioengineering, University of Louisville, Louisville, Kentucky, USA 3 Departments of Radiology, University of Louisville, Louisville, Kentucky, USA 4 Departments of Chemical Engineering, University of Louisville, Louisville, Kentucky, USA 5 Departments of the Molecular Targets Group of the James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA Correspondence to: Mohammad T. Malik, e-mail: tariq.malik@louisville.edu Paula J. Bates, e-mail: paula.bates@louisville.edu Keywords: targeted therapy, nanomedicine, triple negative breast cancer, G-quadruplex, nanoparticles Received: May 11, 2015 Accepted: May 22, 2015 Published: June 03, 2015 ABSTRACT AS1411 is a quadruplex-forming DNA oligonucleotide that functions as an aptamer to target nucleolin, a protein present on the surface of cancer cells. Clinical trials of AS1411 have indicated it is well tolerated with evidence of therapeutic activity, but improved pharmacology and potency may be required for optimal efficacy. In this report, we describe how conjugating AS1411 to 5 nm gold nanospheres influences its activities in vitro and in vivo . We find that the AS1411-linked gold nanospheres (AS1411-GNS) are stable in aqueous and serum-containing solutions. Compared to unconjugated AS1411 or GNS linked to control oligonucleotides, AS1411-GNS have superior cellular uptake and markedly increased antiproliferative/cytotoxic effects. Similar to AS1411, AS1411-GNS show selectivity for cancer cells compared to non-malignant cells. In a mouse model of breast cancer, systemic administration of AS1411-GNS could completely inhibit tumor growth with no signs of toxicity. These results suggest AS1411-GNS are promising candidates for clinical translation.

The purpose of this study was to optimize a new synthesis technique, “DiaSynth,” to produce near-infrared (nIR) absorbing gold nanoplates with prescribed localized surface plasmon resonance (LSPR) wavelengths in higher yields over conventional synthesis methods without the need for laborious purification steps. The molecular weight cut off (MWCO; 3.5, 8, 12, 15, 25 & 50 kDa) of the regenerated cellulose membranes (RCM), temperature (25, 37, 50 & 100 °C) and surface area to volume (SA/Vol) ratio (220, 340 & 470 mm2 ml−1) of the RCM to the gold nanoplate solution were varied during the synthesis process to determine the effect of each parameter on gold nanoplates yield, LSPR peak placement and stability. Results indicate the ability of the RCM to remove ∼99% of the contaminant small gold colloid (

Cervical cancer is caused by human papillomavirus (HPV). The disease develops over many years through a series of precancerous lesions. Cervical cancer can be prevented by HPV-vaccination, screening and treatment of precancer before development of cervical cancer. The treatment of high-grade cervical dysplasia (CIN2+) has traditionally been by cervical conization. Surgical procedures are associated with increased risk of undesirable side effects including bleeding, infection, scarring (stenosis), infertility and complications in later pregnancies. An inexpensive, non-invasive method of delivering therapeutics locally will be favorable to treat precancerous cervical lesions without damaging healthy tissue. The feasibility and safety of a sustained, continuous drug-releasing cervical polymeric implant for use in clinical trials was studied using a large animal model. The goat (Capra hircus), non-pregnant adult female Boer goats (n=7), was chosen due to similarities in cervical dimensions to the human. Estrus was induced with progesterone CIDR® vaginal implants for 14 days followed by the administration of chorionic gonadotropins 48 hours prior to removal of the progesterone implants to relax the cervix to allow for the placement of the cervical implant. Cervical implants, containing 2% and 4% withaferin A (WFA), with 8 coats of blank polymer, provided sustained release for a long duration and were used for the animal study. The ‘mushroom’-shaped cervical polymeric implant, originally designed for women required redesigning to be accommodated within the goat cervix. The cervical implants were well tolerated by the animals with no obvious evidence of discomfort, systemic or local inflammation or toxicity. In addition, we developed a new method to analyze tissue WFA levels by solvent extractions and LS/MS-MS. WFA was found to be localized to the target and adjacent tissues with 12 – 16 ng WFA/g tissue, with essentially no detectable WFA in distant tissues. This study suggests that the goat is a good large animal model for the future development and evaluation of therapeutic efficacy of continuous local drug delivery by cervical polymeric implants to treat precancerous cervical lesions.

Here we report the development of a novel immunosensor-based strategy for label-free detection of viral pathogens by incorporating a sandwich bioassay onto a single-mode, electro-active, integrated optical waveguide (EA-IOW). Our strategy begins with the functionalization of the electro-active waveguide surface with a capture antibody aimed at a specific virus antigen. Once the target antigen is bound to the photonic interface, it promotes the binding of a secondary antibody that has been labeled with a methylene blue (MB) dye. The MB is a redox-active probe whose optical absorption can be electrically modulated and interrogated with high sensitivity by a propagating waveguide mode. In this effort, we have targeted the hemagglutinin (HA) protein from the H5N1 avian influenza A virus to demonstrate the capabilities of the EA-IOW device for detection and quantification of an important antigen. Our initial results for the HA H5N1 influenza virus show a remarkable limit of detection in the pico-molar range.

We present here optical and electrochemical characterization of a sandwich immunosensor assembly on a single-mode, electro-active, integrated optical waveguide platform aimed for implementation a highly sensitive biosensing device.

We describe here a novel immunosensor-based strategy for direct detection of viral pathogens based on sandwich bioassays incorporated on highly sensitive, single-mode, electro-active, integrated optical waveguide platforms.

Fibrotic scarring of the retina, termed proliferative vitreoretinopathy (PVR), can cause permanent visual impairment and blindness following corrective surgery for retinal detachment and/or ocular trauma. We have previously shown that multiple intravitreal injections of dasatinib prevent PVR in an animal model. The aim of this research was to develop injectable sustained release systems for dasatinib, which would be preferred for clinical use over multiple ocular injections. To accomplish this, dasatinib was encapsulated in Poly (lactic-co-glycolic acid) [PLGA] particles via a benchtop spray-drying process. Spray drying parameters were optimized using a taguchi statistical approach to obtain particle size between 0.5 and 1.5 μm. Characterization of two different sets of particles, sub-micron and >1.0 μm in average diameter, respectively, showed that dasatinib release from sub-micron particles lasts 15 days while release from particles with diameters >1.0 μm lasts up to 55 days. Zeta potential measurement of aqueous buffer suspended particles suggests sub-micron particles to be more stable in aqueous environment compared to >1.0 μm particles. Dasatinib released from these particles maintained therapeutic efficacy, as dasatinib incorporated PLGA particles significantly inhibited the contraction of collagen matrices compared to PLGA (control) particles when tested on an in vitro scar contraction assay.

Gold nanoparticles (GNPs) have tremendous potential as cancer-targeted contrast agents for diagnostic imaging. The ability to modify the particle surface with both disease-targeting molecules (such as the cancer-specific aptamer AS1411) and contrast agents (such as the gadolinium chelate Gd(III)-DO3A-SH) enables tailoring the particles for specific cancer-imaging and diagnosis. While the amount of image contrast generated by nanoparticle contrast agents is often low, it can be augmented with the assistance of computer image analysis algorithms. In this work, the ability of cancer-targeted gold nanoparticle&ndash, oligonucleotide conjugates to distinguish between malignant (MDA-MB-231) and healthy cells (MCF-10A) is tested using a T1-weighted image analysis algorithm based on three-dimensional, deformable model-based segmentation to extract the Volume of Interest (VOI). The gold nanoparticle/algorithm tandem was tested using contrast agent GNP-Gd(III)-DO3A-SH-AS1411) and nontargeted c-rich oligonucleotide (CRO) analogs and control (CTR) counterparts (GNP-Gd(III)-DO3A-SH-CRO/CTR) via in vitro studies. Remarkably, the cancer cells were notably distinguished from the nonmalignant cells, especially at nanomolar contrast agent concentrations. The T1-weighted image analysis algorithm provided similar results to the industry standard Varian software interface (VNMRJ) analysis of T1 maps at micromolar contrast agent concentrations, in which the VNMRJ produced a 19.5% better MRI contrast enhancement. However, our algorithm provided more sensitive and consistent results at nanomolar contrast agent concentrations, where our algorithm produced ~500% better MRI contrast enhancement.

In this study we report the development of a novel viral pathogen immunosensor technology based on the electrochemical modulation of the optical signal from a surface plasmon wave interacting with a redox dye reporter. The device is formed by incorporating a sandwich immunoassay onto the surface of a plasmonic device mounted in a micro-electrochemical flow cell, where it is functionalized with a monoclonal antibody aimed to a specific target pathogen antigen. Once the target antigen is bound to the surface, it promotes the capturing of a secondary polyclonal antibody that has been conjugated with a redox-active methylene blue dye. The methylene blue displays a reversible change in the complex refractive index throughout a reduction-oxidation transition, which generates an optical signal that can be electrochemically modulated and detected at high sensitivity. For proof-of-principle measurements, we have targeted the hemagglutinin protein from the H5N1 avian influenza A virus to demonstrate the capabilities of our device for detection and quantification of a critical influenza antigen. Our experimental results of the EC-SPR-based immunosensor under potential modulation showed a 300 pM limit of detection for the H5N1 antigen.

The selective exposure of cancerous tissue to systemically delivered chemotherapeutic agents remains a major challenge facing cancer therapy. To address this question, a near infrared responsive oligonucleotide-coated (AS1411, hairpin, or both) gold nanoplate loaded with doxorubicin is demonstrated to be nontoxic to cells without triggered release, while being acutely toxic to cells after 5 minutes of laser exposure to trigger DOX release. Conjugation of oligonucleotides to the nanoplates is confirmed by an average increase in hydrodynamic diameter of 30.6 nm, an average blue shift of the plasmon resonance peak by 36 nm, and an average −10 mV shift in zeta potential of the particles. DOX loading through intercalation into the hairpin DNA structure is confirmed through fluorescence measurements. For both GNP-Hairpin and GNP-Hairpin-AS1411, ~60% of loaded DOX is released after the first 5 minutes of laser exposure (λ=817 nm), with complete release after two more 5-minute exposures. Preliminary proof of concept is demonstrated in vitro using A549 and MDA-MB-231 cell lines as models for breast and lung cancer, respectively. Exposure of cells to untriggered DOX-loaded conjugate with no laser exposure results in little to no toxicity, while laser-triggered release of DOX causes significant cell death.

Optimal curcumin delivery for medicinal applications requires a drug delivery system that both solubilizes curcumin and prevents degradation. To achieve this, curcumin has been encapsulated in submicrometer chitosan/Tween 20 particles via a benchtop spray-drying process. Spray-drying parameters have been optimized using a Taguchi statistical approach to minimize particle size and to favor spheroid particles with smooth surfaces, as evaluated with scanning electron microscopy (SEM) imaging. Nearly spherical particles with 285 ± 30 nm diameter and 1.21 axial ratio were achieved. Inclusion of curcumin in the spray-drying solution results in complete encapsulation of curcumin within the chitosan/Tween 20 particles. Release studies confirm that curcumin can be released completely from the particles over a 2 h period.

Improving techniques for portable trace analyte collection and pretreatment is of critical concern for security, medical, food and environmental applications. The trend has been to employ MEMS technologies to meet this need as these microfabricated devices offer advantages such as small dead volumes, low power consumption, capacity for large scale manufacture and a commensurate savings with economies of scale. In this work a prototype trace sampling system intended for use with ion mobility spectrometers is presented. The system utilizes a stack of microfabricated preconcentrator plates capable of collecting samples in a sorbent polymer at flow rates up to 30 LPM. The plates are thermally desorbed after an integration period to produce a concentrated vapor plug that is transferred to the detector for analysis. A real-time controller, FPGA and custom electronics are used to manage independent heating of up to 4 of these devices in either constant voltage or temperature modes. The preconcentrators were tested with a commercial Vapor Tracer II IMS against TNT and RDX vapors ranging in concentration from 2.6 PPT to 620 PPT under a variety of conditions. Results are presented on performance of single preconcentrators with RDX, multiple cascaded devices vs. TNT and RDX, with and without a PDMS detector inlet membrane, and to compare sorbent coated and bare devices. The system demonstrated preconcentration factors of 38 with 2.6 PPT RDX and 30 with 13 PPT TNT.

The five-coordinate iron-dithiolate complex (N,N'-4,7-bis-(2'-methyl-2'-mercatopropyl)-1-thia-4,7-diazacyclononane)iron(III), [LFe]+, has been isolated as the triflate salt from reaction of the previously reported LFeCl with thallium triflate. Spectroscopic characterization confirms an S = 1/2 ground state in non-coordinating solvents with room temperature microeff = 1.78 microB and electron paramagnetic resonance (EPR) derived g-values of g1 = 2.04, g2 = 2.02 and g3 = 2.01. [LFe]+ binds a variety of coordinating solvents resulting in six-coordinate complexes [LFe-solvent]+. In acetonitrile the low-spin [LFe-NCMe]+ (g1 = 2.27, g2 = 2.18, and g3 = 1.98) is in equilibrium with [LFe]+ with a binding constant of Keq = 4.7 at room temperature. Binding of H2O, DMF, methanol, DMSO, and pyridine to [LFe]+ yields high-spin six-coordinate complexes with EPR spectra that display significant strain in the rhombic zero-field splitting term E/D. Addition of 1 equiv of triflic acid to the previously reported diiron species (LFe)2O results in the formation of [(LFe)2OH]OTf, which has been characterized by X-ray crystallography. The aqueous chemistry of [LFe]+ reveals three distinct species as a function of pH: [LFe-OH2]+, [(LFe)2OH]OTf, and (LFe)2O. The pKa values for [LFe-OH2]+ and [(LFe)2OH]OTf are 5.4 +/- 0.1 and 6.52 +/- 0.05, respectively.

A series of Hg(II) and Cd(II) homoleptic complexes with mixed donor (O,S and N,S) macrocycles is reported. The macrocyclic oxa thiacrowns 9S2O (1-oxa-4,7-dithiacyclononane) and 18S4O2 (1,10-dioxa-4,7,13,16-tetrathiacyclooctadecane) bind to Hg(II) to form distorted tetrahedral S4 geometries without coordination of the oxygen atoms. In contrast, the two macrocycles coordinate to Cd(II) through all ligand donors to form S4O2 environments. We also report the structure of bis(9N2S (1,4-diaza-7-thiacyclononane))cadmium(II), [Cd(9N2S)2]2+ which shows octahedral coordination in a trans N4S2 environment. Furthermore, two new homoleptic Cd(II) complexes with the related hexadentate macrocycles 18N6 (1,4,7,10,13,16-hexaazacyclooctadecane) and 18S6 (1,4,7,10,13,16-hexathiayclooctadecane) are described. Among the Cd(II) complexes, we highlight a trend in 113Cd NMR that shows progressive upfield chemical shifts as secondary amine donors replace thioether S donors.

Magnetic nanoparticle-supported lipid bilayers (SLBs) constructed around core–shell Fe3O4–SiO2 nanoparticles (SNPs) were prepared and evaluated as potential drug carriers. We describe how an oxime ether lipid can be mixed with SNPs to produce lipid–particle assemblies with highly positive ζ potential. To demonstrate the potential of the resultant cationic SLBs, the particles were loaded with either the anticancer drug doxorubicin or an amphiphilic analogue, prepared to facilitate integration into the supported lipid bilayer, and then examined in studies against MCF-7 breast cancer cells. The assemblies were rapidly internalized and exhibited higher toxicity than treatments with doxorubicin alone. The magnetic SLBs were also shown to increase the efficacy of unmodified doxorubicin.

Hypothesis: A facile, dialysis-based synthesis of stable near infrared (nIR) absorbing plasmonic gold nanoparticles (kmax = 650–1000 nm) will increase the yield of nIR particles and reduce the amount of gold colloid contaminant in the product mixture. Experiments: Chloroauric acid and sodium thiosulfate were reacted using a dialysis membrane as a reaction vessel. Product yield and composition was determined and compared to traditional synthesis methods. The product particle distribution, yield, and partitioning of gold between dispersed product and membrane-adsorbed gold were determined. Findings: The synthesis results in polydisperse particle suspensions comprised of 70% spheroid-like particles, 27% triangular plates, and 3% rod-like structures with a 3% batch-to-batch variation and a prominent nIR absorption band with kmax = 650–1000 nm. The amount of small gold colloid (kmax = 530 nm; d < 10 nm) in the isolated product was reduced by 96% compared to traditional methods. Additionally, 91.1% of the gold starting material is retained in the solution-based nanoparticle mixture while 8.2% is found on the dialysis membrane. The synthesis results in a quality ratio (QR = Abs nIR /Abs 530 ) of 1.7–2.4 (twice that of previous techniques) and 14.3 times greater OD⁄ml yield of the nIR-absorbing nanoparticle fraction.

The iron(III) oxide–alkoxide cluster, di-tetra-n-butylammonium octachloro-tetra(μ3-oxo)-tetra(μ4-oxo)- icosa(μ2-ethoxo)-tetradeca-iron(III), has been isolated and its X-ray crystal structure determined.

Gold nanoparticles (GNPs) with near infrared (NIR) plasmon resonance have been promisingly used in photothermal cancer therapy as a less invasive treatment. Recombinant Protein-G (ProG) was PEGylated to act as a cofactor to immobilize immunoglobulins (IgGs) on GNPs by the F c region, resulting in optimal orientation of IgGs for efficient cancer targeting. In-vitro studies showed that HER-2 overexpressing breast cancer cells, SK-BR-3, were efficiently targeted and ablated at a laser power of 900 J/cm 2 (5 W/cm 2 for 3 min). However, as a means of enhancing treatment efficacy by increasing cellular sensitivity to chemotherapeutic agents, we showed that GNP exposure to lower power laser resulted in small disruptions of cell membrane due to localized hyperthermia. This did not lead to cell death but provided a mechanism for killing cancer cells by providing enhanced uptake of drug molecules thus leading to a new avenue for hyperthermia-anticancer drug combined cancer therapeutics. From the Clinical Editor PEGylated recombinant Protein-G was used as a cofactor to optimize the orientation of IgGs providing “target seeking” properties to gold nanoparticles used in photothermal cancer therapy. The system demonstrated excellent properties in cancer therapy, with the hope and expectation of future clinical translation.

Curcumin is an extract of turmeric, and is an effective reactive oxygen species scavenger, with potential anti-cancer benefits. In this study, we examined the effects of curcumin on membrane bilayer permeability, fusion, anisotropy, hydrodynamic radius and negative staining EM using two lipid vesicle delivery systems: 1) 99% Soy phosphatidylcholine (Soy PC) and 2) DMPC/DPPG/Cholesterol (1:1:0.7 mol/mol/mol) (MPC). Curcumin was added to these two vesicle populations at 10:1, 50:1, and 100:1 (lipid mol/curc mol). The structure of curcumin suggests it would most likely intercalate into the head group region of the membrane bilayer, and thus our hypothesis was that the unsaturated fatty acids of Soy PC vesicles would accommodate curcumin with less membrane perturbation than the saturated MPC vesicles. Curcumin increased membrane permeability to carboxyfluorescein leakage (CF) in both Soy PC and MPC small unilamellar vesicles in a concentration-dependent manner; however, Soy PC vesicles were 35% more permeable to CF than MPC vesicles. The fusion of the Soy PC and MPC was examined by vesicle mixing using the Tb/DPA-assay. Both Soy PC and MPC vesicles fused within seconds of addition, and the rate of fusion was dependent on buffer calcium concentration. Curcumin had membrane concentration-dependent effects on the fluorescence anisotropy of DPH-PC and TMA-DPH Soy PC and MPC vesicles. Lipid vesicle hydrodynamic radius and TEM negative stained vesicles indicate a unimodal distribution for Soy PC vesicles (r = 100-120 nm), while MPC vesicles had a bimodal distribution (r = 100-130 nm and 3000-4000 nm). Thus curcumin can more readily intercalate into more unsaturated lipid vesicle bilayers, and we conclude that for maximal delivery of curcumin to cells using a liposomal therapy, a more unsaturated vesicle system is suggested.

For optical diagnosis of the human body, using near infrared (NIR) has several advantages: NIR penetrates into the tissue deeper than UV or visible light, and in NIR most of the tissue-originated fluorescence may be avoided. Although NIR fluorophores are valuable, only a few can be used for humans and they have relatively low quantum yields. If the fluorescence emission of NIR fluorophores can be artificially enhanced, it can increase the sensitivity of optical diagnosis. In addition, conditionally emitted contrast agents as in Forster resonance energy transfer (FRET) or molecular beacon can be developed. One way of artificially changing fluorescence is by applying an electric field to the fluorophore. An excellent way of generating the field is via the plasmon field by gold nanoparticles (GNPs) upon the receipt of the excitation light of the fluorophore to be used. In this paper, the mechanism of the fluorescence manipulation for an NIR fluorophore, Cypate, by GNPs is studied both theoretically and experimentally.

Nanoparticles are currently being intensively studied for in vivo molecular imaging because of their unique and beneficial properties. Among these particles, some metal particles possess strong surface plasmon fields that can effectively alter fluorescence. Using this fluorescence alteration, an NIR fluorophore based, nanosized contrast agent for breast cancer diagnosis is being developed. The fluorophore is conjugated to gold nanoparticles (GNP) viaa short spacer whose lengthwas specially adjusted to have the strong plasmon field to quench the fluorescence. The spacer also has a special molecular sequence that can be cleaved by an enzyme secreted by targeted cancer cells. Normally, the entity does not fluoresce. If it is delivered to the cancer site, the short spacer would be cleaved by the enzyme secreted by the cancer cell at which point the fluorescence would be restored. This entity can incorporate a cancer targeting molecule for a cancer specific delivery. The entity specifically targets cancer cells and fluoresce only when the spacer is cleaved by a specific cancer secreting biomolecule, providing dual specificity for cancer diagnosis. In the future, this entity will be combined with cancer drugs for seamless detection and personalized therapy.

The oxygen sensitivity of two related iron(III) dithiolate complexes of the ligand [4,7-bis-(2'-methyl-2'-mercatopropyl)-1-thia-4,7-diazacyclononane], (bmmp-TASN)FeCN (1) and (bmmp-TASN)FeCl (2), has been examined. Oxygen exposure of the low-spin complex 1 yields the disulfonate complex (bmmp-O6-TASN)FeCN (3) as an olive-green solid with characteristic peaks in the IR spectrum at 1262, 1221, 1111, 1021, 947, 800, and 477 cm(-1). The corresponding nickel dithiolate, (bmmp-TASN)Ni (4), yields the related disulfonato derivative, (bmmp-O6-TASN)Ni (5) upon addition of H2O2 (IR bands at 1258, 1143, 1106, 1012, 800, and 694 cm(-1). Oxygen exposure of the high-spin complex 2 results in disulfide formation and decomplexation of the metal with subsequent iron-oxo cluster formation. Complexes 1 and 2 were examined using density functional theory calculations. A natural bond order/natural localized molecular orbital covalency analysis reveals that the low-spin complex 1 contains Fe-Sthiolate bonds with calculated covalencies of 75 and 86%, while the high-spin complex 2 contains Fe-Sthiolate bonds with calculated covalencies of 11 and 40%. The results indicate the degree of covalency of the Fe-S bonds plays a major role in determining the reaction pathway associated with oxygen exposure of iron thiolates. The X-ray structures of 1, 4, and 5 are reported.

Advances in microelectromechanical systems (MEMS) continue to empower researchers with the ability to sense and actuate at the micro scale. Thermally driven MEMS components are often used for their rapid response and ability to apply relatively high forces. However, thermally driven MEMS often have high power consumption and require physical wiring to the device. This work demonstrates a basis for designing light-powered MEMS with a wavelength specific response. This is accomplished by patterning surface regions with a thin film containing gold nanoparticles that are tuned to have an absorption peak at a particular wavelength. The heating behavior of these patterned surfaces is selected by the wavelength of laser directed at the sample. This method also eliminates the need for wires to power a device. The results demonstrate that gold nanoparticle films are effective wavelength-selective absorbers. This “hybrid” of infrared absorbent gold nanoparticles and MEMS fabrication technology has potential applications in light-actuated switches and other mechanical structures that must bend at specific regions. Deposition methods and surface chemistry will be integrated with three-dimensional MEMS structures in the next phase of this work. The long-term goal of this project is a system of light-powered microactuators for exploring cellular responses to mechanical stimuli, increasing our fundamental understanding of tissue response to everyday mechanical stresses at the molecular level.

The title compound, [Ni(C10H22N2S2)], contains a square-planar Ni center coordinated by the tetra­dentate ligand 3,3′-[ethane-1,2-diylbis(methyl­imino)]dipropane-1-thiol­ate. Upon chelation, the N2S2 ligand generates one five-membered chelate ring containing the N donors and two six-membered chelate rings in chair conformations, each containing one N and one S donor. The cis S donors, which are not directly linked together, form an acute S—Ni—S angle of 82.965 (18)° due to ligand constraints.