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Auburn University, AL, United States

Yang C.,Ryerson University | Uertz J.,CytoViva | Chithrani D.B.,Ryerson University | Chithrani D.B.,Li Ka Shing Knowledge Institute
Nanomaterials | Year: 2016

Nanoparticles (NPs) can be used to overcome the side effects of poor distribution of anticancer drugs. Among other NPs, colloidal gold nanoparticles (GNPs) offer the possibility of transporting major quantities of drugs due to their large surface-to-volume ratio. This is while confining these anticancer drugs as closely as possible to their biological targets through passive and active targeting, thus ensuring limited harmful systemic distribution. In this study, we chose to use bleomycin (BLM) as the anticancer drug due to its limited therapeutic efficiency (harmful side effects). BLM was conjugated onto GNPs through a thiol bond. The effectiveness of the chemotherapeutic drug, BLM, is observed by visualizing DNA double strand breaks and by calculating the survival fraction. The action of the drug (where the drug takes effect) is known to be in the nucleus, and our experiments have shown that some of the GNPs carrying BLM were present in the nucleus. The use of GNPs to deliver BLM increased the delivery and therapeutic efficacy of the drug. Having a better control over delivery of anticancer drugs using GNPs will establish a more successful NP-based platform for a combined therapeutic approach. This is due to the fact that GNPs can also be used as radiation dose enhancers in cancer research. © 2016 by the authors; licensee MDPI, Basel, Switzerland.

Cruje C.,Ryerson University | Yang C.,Ryerson University | Uertz J.,CytoViva | Van Prooijen M.,Princess Margaret Cancer Center | And 2 more authors.
RSC Advances | Year: 2015

Nanoscale gold particles are being used as a radiation dose enhancer in cancer research. The purpose of this study was to optimize the uptake of polyethylene glycol (PEG) functionalized gold nanoparticles (GNPs) for an enhanced therapeutic effect during radiation therapy. PEG is widely used in providing NPs with stealth properties, thus prolonging blood circulation times. However, PEG minimizes PEG-GNP interaction with cell surface ligands resulting in significantly lower in vitro cellular uptake. As intracellular localization of GNPs maximizes its therapeutic enhancement, there is a need to improve the uptake of PEG-GNPs. To enhance uptake, RGD peptide containing an integrin binding domain was conjugated along with PEG. Spherical GNPs of diameters 14 and 50 nm and PEG chain lengths of 2 kDa were used for the study. Nanoparticles functionalized with both RGD peptide and PEG had higher uptake than NPs functionalized with PEG alone. The enhancement in uptake was higher for 14 nm NPs as compared to 50 nm NPs. Our radiation therapy results showed that smaller NPs conjugated with PEG and RGD peptides have a three-fold therapeutic enhancement as compared to larger NPs in MDA-MB-231 cells at clinically relevant 6 MV energy. This study will shed light on clinical use of GNPs in radiation therapy in the near future. © The Royal Society of Chemistry.

More S.S.,University of Minnesota | Beach J.M.,CytoViva | Vince R.,University of Minnesota
Investigative Ophthalmology and Visual Science | Year: 2016

Purpose: To describe a spectral imaging system for small animal studies based on noninvasive endoscopy of the retina, and to present time-resolved spectral changes from live Alzheimer's mice prior to cognitive decline, corroborating our previous in vitro findings. Methods: Topical endoscope fundus imaging was modified to use a machine vision camera and tunable wavelength system for acquiring monochromatic images across the visible to near-infrared spectral range. Alzheimer's APP/PS1 mice and age-matched, wild-type mice were imaged monthly from months 3 through 8 to assess changes in the fundus reflection spectrum. Optical changes were fit to Rayleigh light scatter models as measures of amyloid aggregation. Results: Good quality spectral images of the central retina were obtained. Short-wavelength reflectance from Alzheimer's mice retinae showed significant reduction over time compared to wild-type mice. Optical changes were consistent with an increase in Rayleigh light scattering in neural retina due to soluble Aβ1–42 aggregates. The changes in light scatter showed a monotonic increase in soluble amyloid aggregates over a 6-month period, with significant build up occurring at 7 months. Conclusions: Hyperspectral imaging technique can be brought inexpensively to the study of retinal changes caused by Alzheimer's disease progression in live small animals. A similar previous finding of reduction in the light reflection over a range of wavelengths in isolated Alzheimer's mice retinae, was reproducible in the living Alzheimer's mice. The technique presented here has a potential for development as an early Alzheimer's retinal diagnostic test in humans, which will support the treatment outcome. © 2016, Association for Research in Vision and Ophthalmology Inc. All rights reserved.

Rudzinski W.E.,Texas State University | Krauss L.,CytoViva
Nanomedicine | Year: 2015

Aim: To develop insulin loaded deoxycholic acid conjugated PEGylated polyhydroxybutyrate co-polymeric nanoparticles and carry out in vitro and in vivo testing of enteric coated granules comprising these nanoparticles. Materials & methods: Insulin loaded nanoparticles were prepared and characterized in vitro. Cellular uptake was studied using hyperspectral and live cell confocal microscopy. Enteric coated granules of nanoparticles were fed orally to diabetic rats and the pharmacokinetic and pharmacodynamic parameters were evaluated. Results: Ultra small (10 nm) nanoparticles with polydispersity index of 0.299 were obtained. The enteric coated granules showed a negligible insulin release in acidic pH, but released insulin in alkaline environment. High cellular uptake was observed and nanoparticles were able to maintain the blood glucose levels up to 24 h. Conclusion: These enteric-coated nanoparticle granules sustained the release of insulin and showed enhanced insulin bioavailability. Hence, these may serve as a platform device for oral insulin delivery with extended release. © 2015 Future Medicine Ltd.

Ethylene-co-acrylic acid (EAA) and ethylene-co-methacrylic acid ionomer (EMAZ) copolymers were used as compatibilizers for polyethylene-graphene nanocomposites generated by melt mixing. At 5 wt% content, the EAA compatibilizer enhanced the tensile modulus of PE by 40 % and shear modulus by >300 % (1 rad/s) due to efficient dispersion of graphene platelets which helped in effective stress transfer. These also resulted in enhanced thermal stability for PE-EAA-G nanocomposite as compared to nanocomposite with EMAZ. The properties of the nanocomposites were significantly better than the conventional nanocomposites based on layered silicate materials. Mapping of the component distribution in the nanocomposites was demonstrated by using hyperspectral imaging. The nanocomposite with EAA exhibited higher extent of spectral signal mixing due to better mixing of filler and compatibilizer in PE matrix. On the other hand, nanocomposite with EMAZ had no spectral mixing as the components did not mix optimally with each other. The DSC thermogram for this nanocomposite also exhibited a small shoulder at low temperature probably due to immiscibility of the compatibilizer with the matrix polymer. The hyperspectral imaging and mapping was thus demonstrated to be a useful method for determination of component distribution in complex nanocomposite systems. © 2014, Springer-Verlag Berlin Heidelberg.

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