Ionizing radiation is widely used as a therapeutic tool. There is interest in the use of metallic nanoparticles in the role of radiation sensitizer. We have previously described an experimental system in which plasmid DNA condensed with basic oligopeptides functions as a model for chromatin. This system reproduces well the yields of DNA radiation damage observed in mammalian cells. We aimed here to extend this model system by including silver nanoparticles. Spectroscopy, light scattering, gel electrophoresis, sedimentation, and atomic force microscopy all indicate that anionic lipoate-coated silver nanoparticles can be co-aggregated with DNA by using a tetra-arginine peptide. The resulting co-aggregates are micron sized, of the same order as the nuclei of mammalian cells. Increasing the ionic strength results in disaggregation enabling recovery of the freed DNA after which it can be subjected to a wide variety of assays to characterize the radiosensitizing effects of the silver nanoparticles. This self-assembled system of three ionically bound components (nanoparticle, DNA, and peptide) offers the advantage of avoiding the complexity of forming and breaking covalent bonds between the nanoparticles and DNA.

X-irradiation has extensive applications in therapy and considerable attention has been devoted to the radiosensitizing properties of nanoparticles composed of high atomic number elements, particularly gold. Low energy electrons and/or heterogenous catalysis are widely suspected to be involved in radiosensitization, but there is uncertainty about their contributions. Because of their greater surface area to volume ratio relative to spherical particles per unit mass of gold, nanostars permit more low energy electrons to escape and possess an increased catalytic activity. Condensed DNA represents a highly useful model for mammalian chromatin, particularly with respect to the types and yields of DNA damage produced by ionizing radiation. Here we describe the incorporation of spherical gold nanoparticles and of gold nanostars into a condensed DNA model system. The resulting self-assembled micron-sized co-aggregates involve an intimate association between gold and DNA, maximizing the opportunity for the production of DNA damage. After increasing the ionic strength, the co-condensate becomes disaggregated and the DNA is available for subsequent assays. This model system provides a previously unavailable tool for examining the mechanisms of radiosensitization of DNA damage by gold nanoparticles with implications for possible applications in radiotherapy.

The basic peptide N-acetyl-tetra-L-arginine-amide has been reported to act as a DNA condensing agent. This peptide also aggregated lipoate coated gold nanoparticles (AuNPs). In the absence of the peptide, the anionic DNA and AuNPs showed no evidence of interaction with one another. However, when a solution containing both DNA and AuNPs was treated with the peptide, the sedimentation behavior, UV-visible spectroscopy, scanning electron microscopy, and atomic force microscopy all revealed that they can be co-aggregated. Dynamic light scattering and the sedimentation behavior of these co-aggregated particles both indicated a mean particle size of ca. 3 mu m. The DNA could be released and assayed for damage after increasing the ionic strength. This constitutes a convenient model system with which to quantify radiosensitization by AuNPs. Using these co-aggregates as targets for gammas and X-rays, the presence of AuNPs resulted in a 1.3- to 1.6-fold increase in the DNA single strand break (SSB) yield produced by these ionizing radiations.

Glioblastoma multiforme (GBM) is a glioma and the most aggressive type of brain tumor with a dismal average survival time, despite the standard of care. One promising alternative therapy is boron neutron capture therapy (BNCT), which is a noninvasive therapy for treating locally invasive malignant tumors, such as glioma. BNCT involves boron-10 isotope capturing neutrons to form boron-11, which then releases radiation directly into tumor cells with minimal damage to healthy tissues. This therapy lacks clinically approved targeted blood–brain-barrier-permeating delivery vehicles for the central nervous system (CNS) entry of therapeutic boron-10. Gold nanoparticles (GNPs) are selective and effective drug-delivery vehicles because of their desirable properties, facile synthesis, and biocompatibility. This review discusses biomedical/therapeutic applications of GNPs as a drug delivery vehicle, with an emphasis on their potential for carrying therapeutic drugs, imaging agents, and GBM-targeting antibodies/peptides for treating glioma. The constraints of GNP therapeutic efficacy and biosafety are discussed.

The experimental radiation therapy involving thermal neutron capture by boron (boron neutron capture therapy, BNCT) offers the advantage of high-LET ions with ranges on the order of a cell nucleus. Efforts to implement it have encountered serious difficulties. A practical model system would be able to address the underlying mechanisms of DNA damage and also calibrate Monte Carlo simulations. We describe the characterization of a plasmid-based model in which DNA condensed with a tetra-arginine peptide is co-aggregated with mercapto-closo-dodecaborate (BSH) coated gold nanoparticles (AuNPs). Condensed DNA is an excellent model for cellular chromatin, and the AuNPs are able to function as boron carriers and neutron dosimeters. Data from light scattering, UV-visible spectroscopy, fluorescence spectroscopy, sedimentation behavior, gel electrophoresis, and atomic force microscopy all indicate that the basic peptide acts to co-aggregate the two polyanionic species DNA and BSH-coated AuNPs. This aggregation is easily reversed by an increase in ionic strength to free the plasmid for subsequent assay. We argue that this three-component system is simpler, more convenient, and more flexible than other models requiring covalent attachments between DNA, boron, and/or gold.

We examined DNA binding and condensation by AcCR4NH2 and CR4NH2 ligands. By this approach, we can model physical DNA damage by ionizing radiation. The binding constant was 1 x 106 L mol-1 at low ionic strength (ca. 10 mmol L-1 sodium ions) and the resulting condensate size was ca. 1 & mu;m. Given the similar base pair concentrations of ca. 250 mmol L-1 in condensed DNA and chromatin, DNA damage yields by ionizing irradiation in condensates with related oligoarginine ligands are comparable to those in eukaryotic nuclei. Therefore, with the benefit of these results, we can envisage an experimental system suitable for modeling DNA damage by ionizing radiation because it reproduces well the essential conditions in cell nuclei that affect this damage, particularly the high concentrations of DNA and protein in chromatin and the resulting highly efficient radical scavenging environment.

PURPOSE:Peritoneal carcinomatosis (PC), metastasized from colorectal cancer (CRC), remains a highly lethal disease. Outcomes of PC is significantly influenced by the amount of intra-abdominal tumor burden and therefore diagnostic tests that facilitate earlier diagnosis could improve PC treatment and patient outcomes.EXPERIMENTAL DESIGN:Using mass-spectrometry-based proteomics, we characterized the protein features of circulating exosomes in the context of CRC PC, CRC with liver metastasis, and primary CRC limited to the colon. We profiled exosomes isolated from patient plasma to identify exosome-associated protein cargoes released by these cancer types.RESULTS:Analysis of the resulting data identified metastasis-specific exosome protein signatures. Bioinformatic analyses confirmed enrichment of proteins annotated to vesicle-associated processes and intracellular compartments, as well as representation of cancer hallmark functions and processes.CONCLUSION AND CLINICAL RELEVANCE:This research yielded distinct protein profiles for the CRC patient groups and suggests the utility of plasma exosome proteomic analysis for a better understanding of PC development and metastasis.

We demonstrate the application of nanoparticle tracking analysis (NTA) for the quantitative characterization of gold nanostars (GNSs). GNSs were synthesized by the seed-mediated growth method using triblock copolymer (TBP) gold nanoparticles (GNPs). These GNPs (.:-; 10 nm) were synthesized from Au3+ (approximate to 1 mM) in aqueous F127 (w/v 5%) containing the co-reductant ascorbic acid (approximate to 2 mM). The GNS tip-tocore aspect ratio (AR) decreased when higher concentrations of GNPs were added to the growth solution. The AR dependency of GNSs on Au3+/Au(seed) concentration ratio implies that growth is partly under kinetic control. NTA measured GNS sizes, concentrations, and relative scattering intensities. Molar absorption coefficients similar to 10(9) - 10(10) M-1 cm(-1) (epsilon 400 (nm)) for each batch of GNSs were determined using the combination of extinction spectra and NTA concentrations for heterogeneous samples. NTA in combination with UV-vis was used to derive the linear relationships: (1) hydrodynamic size versus localized surface plasmon peak maxima; (2) epsilon 400 (nm) versus localized surface plasmon peak maxima; (3) epsilon 400 (nm) versus hydrodynamic size. NTA for quantitative characterization of anisotropic nanoparticles could lead to future applications, including heterogeneous colloidal catalysis.

OBJECTIVES:This study aimed to use a laboratory model to evaluate the efficacy of an experimental bleaching agent.MATERIALS AND METHODS:The model used human extracted molars that were treated and measured for bleaching efficacy. Teeth (n = 50) were distributed into 5 groups: Negative control (NC): immersion in water for 8 hours; Nanofibers (NFs): Experimental titanium dioxide nanofibers with stirring and light activation for 8 hours; Whitestrips (WS): Crest 3D White Glamorous White Whitestrips, 2 applications daily for 30 minutes, 14 days; 1% hydrogen peroxide (HP) standard: 1% hydrogen peroxide for 8 hours; and 30% HP standard: 30% hydrogen peroxide for 8 hours. Instrumental measurements were performed using a spectrophotometer. Results were recorded at baseline, 1-day post-bleaching, and 1-week post-bleaching. Kruskal-Wallis procedure was used to determine differences in color change. Pearson correlation was used to evaluate the relationship between visual and instrumental measurements. Tests of hypotheses were 2-sided with alpha = 0.05.RESULTS:There was no significant difference in color parameters (L1, a1, b1, and shade guide units [SGU]) at baseline (p > 0.05). There was a significant difference among the groups for overall color change (ΔE*ab) and change in shade guide units (ΔSGU) at 1-day and 1-week post-bleaching (p < 0.05). The higher the HP concentration, the higher the color change as expressed in ΔSGU and ΔE*ab. The negative control exceeded the perceptibility threshold of ΔE* = 1.2 regardless of time point. NFs showed a decrease in chroma, but were not statistically different compared to the negative control.CONCLUSIONS:The laboratory model was successful in screening an experimental bleaching agent.

The compound 4-dihydroxyboryl-l-phenylalanine (BPA) has found use in clinical trials of boron neutron capture therapy (BNCT). Here, we have examined the interaction with DNA of an amide-blocked BPA derivative of hexa-l-arginine (Ac-BPA-Arg6-NH2). Physical and spectroscopic assays show that this peptide binds to and condenses DNA. The resulting condensates are highly resistant to the effects of nuclease incubation (68-fold) and gamma (38-fold) irradiation. Radioprotection was modeled by Monte Carlo track structure simulations of DNA single strand breaks (SSBs) with TOPAS-nBio. The differences between experimental and simulated SSB yields for uncondensed and condensed DNAs were ca. 2 and 18%, respectively. These observations indicate that the combination of a plasmid DNA target, the BPA-containing peptide, and track structure simulation provides a powerful approach to characterize DNA damage by the high-LET radiation associated with neutron capture on boron.

We aimed to determine the mechanism of epithelial–mesenchymal transition (EMT)-induced stemness in cancer cells. Cancer relapse and metastasis are caused by rare stem-like cells within tumors. Studies of stem cell reprogramming have linked let-7 repression and acquisition of stemness with the EMT factor, SNAI1. The mechanisms for the loss of let-7 in cancer cells are incompletely understood. In four carcinoma cell lines from breast cancer, pancreatic cancer, and ovarian cancer and in ovarian cancer patient-derived cells, we analyzed stem cell phenotype and tumor growth via mRNA, miRNA, and protein expression, spheroid formation, and growth in patient-derived xenografts. We show that treatment with EMT-promoting growth factors or SNAI1 overexpression increased stemness and reduced let-7 expression, while SNAI1 knockdown reduced stemness and restored let-7 expression. Rescue experiments demonstrate that the pro-stemness effects of SNAI1 are mediated via let-7. In vivo, nanoparticle-delivered siRNA successfully knocked down SNAI1 in orthotopic patient-derived xenografts, accompanied by reduced stemness and increased let-7 expression, and reduced tumor burden. Chromatin immunoprecipitation demonstrated that SNAI1 binds the promoters of various let-7 family members, and luciferase assays revealed that SNAI1 represses let-7 transcription. In conclusion, the SNAI1/let-7 axis is an important component of stemness pathways in cancer cells, and this study provides a rationale for future work examining this axis as a potential target for cancer stem cell-specific therapies.

The amino acid derivative 4-borono-L-phenylalanine (BPA) has been used in the radiation medicine technique boron neutron capture therapy (BNCT). Here we have characterized its interaction with DNA when incorporated into a positively charged hexa-L-arginine peptide. This ligand binds strongly to DNA and induces its condensation, an effect which is attenuated at higher ionic strengths. The use of an additional tetra-L-arginine ligand enables the preparation of a DNA condensate in the presence of a negligible concentration of unbound boron. Under these conditions, Monte Carlo simulation indicates that >85% of energy deposition events resulting from thermal neutron irradiation derive from boron fission. The combination of experimental model systems and simulations that we describe here provides a valuable tool for accurate track structure modeling of the DNA damage produced by the high LET particles involved in BNCT.

AIM:Gold nanorods (GNRs) have gained interest as a promising carrier for antibiotics. Gold nanorods may reduce the development of antimicrobial resistance in certain microbial species. Although applications of GNRs to mitigate oral biofilms are under development, their use in the oral cavity may have adverse effects. The aim of this study was to evaluate the potential penetration of GNRs into the tooth enamel structure using confocal laser scanning microscopy (CLSM) and scanning transmission electron microscopy (STEM).MATERIALS AND METHODS:Our approach was to synthesize GNRs with cationic [cetyltrimethylammoniumbromide (CTAB)] and anionic [11-mercaptoundecanoic acid (MUDA)] surface coatings. We hypothesized that penetration would be surface coating dependent.RESULTS:Regardless of the chemical modification of the GNRs of size ∼20 nm × 8 nm, exposure of these materials did not result in superficial penetration into the enamel.CONCLUSION:Within the limitations of this study, it is concluded that the use of CLSM and STEM is a feasible approach to investigate the penetration of nanomaterials into the tooth structure.CLINICAL SIGNIFICANCE:Exposure of the enamel with chemically modified GNRs of size ∼20 nm × 8 nm will not result in superficial penetration into the enamel.

Advances in nanotechnology and 3D printing are making significant impacts on dentistry. The purpose of this study was to synthesize titanium oxide nanofibers and gold-coated titanium oxide nanofibers, disperse them into the resin matrix to 3D print composite discs and evaluate the change in surface roughness associated with repeated UV-light activation over time. The infusion of nanomaterials and prolonged UV-light activation did not adversely affect the surface roughness properties of the 3D printed material.

Advances in nanotechnology are making a significant impact on dentistry. This study evaluated the change in oxidation potential of synthesized TiO2 nanofibers (NFs) compared to commercial TiO2 nanoparticles (NPs). TiO2 NFs had higher oxidation potential compared to TiO2 NPs when activated with ultraviolet (UV) light using a yellow tartrazine dye. Therefore, it is expected that replacement of TiO2 NPs to NFs as a photocatalyst in bleaching systems could enhance the efficacy and speed of the bleaching process.

The conventional supermarket represents an important public access to a wide variety of food that is vital for healthy families. The supermarket is also a location where food, the public, and pathogens can meet. The purpose of this study was to develop and test a hypothesized norovirus transmission pathway via reusable grocery bags (RGBs) within a conventional grocery supermarket. An RGB was inoculated with a surrogate virus to assess potential transport of pathogens within a grocery store. Volunteer shoppers were given an RGB sprayed with a surrogate (bacteriophage MS2) upon entry to a grocery store. A surrogate is defined in this study as an organism, particle, or substance that is used to study the fate and transport of a pathogen in a specific environment (Sinclair, Rose, Hashsham, Gerba, & Haas, 2012). The study personnel swabbed all surfaces touched by the volunteer shopper to recover the MS2 surrogate. The data show that MS2 spread to all surfaces touched by the shopper; the highest concentration occurred on the shopper's hands, the checkout stand, and the clerk's hands. The high concentration of MS2 on hands justify a recommendation for in-store hand hygiene as a primary preventive measure against transmission of infectious pathogens. The high concentrations on the checkout stand justify a secondary recommendation for surface disinfection and public education about washing RGBs.

Optimization of physicochemical properties of TiO2 anatase for organophosphorus remediation remains challenging. One approach is to use anatase nanofibers, prepared from hydrothermally synthesized titanates. Charge densities and potentials of anatase nanofibers were determined from atomic force microscopy force-curve measurements using the modified Derjaguin, Landau, Verwey, Overbeek theory, which includes roughness and hydration forces, in the pH range 4-9. Calculated values were -0.007 to -0.03 C m(-2) and -70 to -150 mV, respectively. In contrast, at neutral pH, the magnitudes of diffuse layer surface charge densities and potentials have a minimum in anatase nanoparticles. These observations and zeta-potential results suggest that nanofiber surfaces are more acidic compared with nanoparticles. This is consistent with nanofibers having similar to 3-fold higher adsorption for organophosphorus methyl parathion (pH approximate to 7). The resulting adsorption includes contributions from (1) charge accumulation at local coordination sites caused by the morphological roughness; (2) greater crystallographic nanoscale variations; and (3) active site competition between parent and daughter species. The structural features of nanofibers have potential applications in catalysis and sequestration of organophosphorus compounds.

Objective: Curcumin (diferuloylmethane) has promising anti-cervical cancer properties but requires a stabilizing complex such as the Pluronic triblock copolymer gold nanoparticle (GNP). The objectives were to study cytotoxicity of curcumin and to determine the effect of copolymer GNPs curcumin complex on cancer cell necrosis. Materials and Methods: The HeLa cells were maintained in Eagle Minimal Essential Medium, fetal bovine serum, and antibiotics, and passaged until 60 % confluency was reached. The cells were exposed to either: (1) control medium, (2) 50 mu M curcumin, (3) 100 mu M curcumin, (4) 50 mu M curcumin with copolymer GNPs complex, or (5) 100 mu M curcumin with copolymer GNPs complex. The treated cells were incubated at 37 degrees C with 5% CO2 in air for 24 hours, and analyzed for viability, apoptosis or necrosis using the dual stains fluorescence procedure. Results: A dose-dependent increase in the HeLa necrosis was observed with increasing curcumin concentrations. Cytotoxic effect was decreased by five- to ten-fold when the curcumin was complexed with copolymer GNPs. There were more apoptotic HeLa cells at the higher concentration of curcumin but combination with copolymer GNPs resulted in decreased apoptosis. Cell viability was higher in curcumin with copolymer GNPs (74.4 +/- 4.8 versus 2.3 +/- 2.2 % live, mean SEM, with and without copolymer GNPs, respectively). Conclusion: Curcumin increased HeLa cancer cell necrosis but its cytotoxicity was decreased by copolymer GNPs. The results suggested that this specific copolymer GNP did not enhance the curcumin bioavailability in cultured cells possibly due to formation of copolymer GNP aggregates.

A stable and highly sensitive gas ionization sensor (GIS) constructed from vertically aligned, conductive yttrium–doped ZnO nanorod (YZO NR) arrays is demonstrated. The conductive YZO NRs are synthesized using a facile one-pot hydrothermal method. At higher Y/Zn molar ratio, the aspect ratio of the YZO NRs is increased from 11 to 25. Doping with yttrium atoms decreases the electrical resistivity of ZnO NRs more than 100 fold. GIS measurements reveal a 6-fold enhancement in the sensitivity accompanied with a significant reduction in breakdown voltage from the highly conductive YZO NRs. Direct correlations between the resistivity of the NRs and GIS characteristics are established.