PEG-coated Gold Nanoparticles Research Articles

Assessing the toxicity of one-step-synthesized PEG-coated gold nanoparticles: in vitro and in vivo studies.

To evaluate the in vitro and in vivo toxicities of polyethylene glycol-coated gold nanoparticles synthesized using a one-step process. Gold nanoparticles were prepared via a co-precipitation method using polyethylene glycol, and the synthesis product was characterized. For the in vitro evaluation, a flow cytometry analysis with Annexin V and iodide propidium staining was used to assess cytotoxicity in MG-63 cells labeled with 10, 50, and 100µg/mL of nanoparticle concentration. For the in vivo evaluation, nanoparticles were administered intraperitoneally at a dose of 10mg/kg dose in 10-week-old mice. Toxicity was assessed 24 hours and 7 days after administration via histopathological analysis of various tissues, as well as through renal, hepatic, and hematopoietic evaluations. Synthesized nanoparticles exhibited different hydrodynamic sizes depending on the medium: 51.27±1.62nm in water and 268.12±28.45nm (0 hour) in culture medium. They demonstrated a maximum absorbance at 520nm and a zeta potential of -8.419mV. Cellular viability exceeded 90%, with less than 3% early apoptosis, 6% late apoptosis, and 1% necrosis across all labeling conditions, indicating minimal cytotoxicity differences. Histopathological analysis highlighted the accumulation of nanoparticles in the mesentery; however, no lesions or visible agglomeration was observed in the remaining tissues. Renal, hepatic, and hematopoietic analyses showed no significant differences at any time point. Polyethylene glycol-coated gold nanoparticles exhibit extremely low toxicity and high biocompatibility, showing promise for future studies.

Design and fabrication of alginate hydrogel nanohybrid as a promising cancer treatment.

Basal cell carcinoma (BCC) is the most common form of skin cancer and the most frequently occurring form of all cancers, affecting sun-exposed areas like the face. Surgery is the main treatment, focusing on safe and minimally invasive methods for better outcomes. Technology has enabled the development of artificial skin substitutes for tissue repair. Tissue engineering uses scaffolds to create functional replacements. This project aims to create an alginate-based hydrogel with PEG-coated gold nanoparticles. The project extensively explored the modification of alginate hydrogels with PEG-coated gold nanoparticles, involving the synthesis of gold nanoparticles, their integration with the polymer, and the subsequent preparation of the concentrated hybrid hydrogel. Utilizing various physicochemical techniques, such as UV-visible spectroscopy, transmission electron microscopy, dynamic light scattering, zeta potential analysis, scanning electron microscopy, and Fourier transform infrared spectroscopy, the fabrication process was optimized and characterized. The successful synthesis of the hybrid biomaterial was achieved through robust and highly reproducible methods. The MTT assay results offered valuable insights into the biocompatibility and safety of the PEG-coated gold nanoparticle-loaded alginate-based films. The incorporation of PEG-coated gold nanoparticles allowed for potential drug loading on the nanoparticle surface and, consequently, within the hydrogel. Cellular assays were conducted to assess the potential applications of this novel biomaterial. The addition of polyethylene glycol made it possible to load different drugs onto the gold nanoparticles and also within the hydrogel. This makes it a promising choice for potential uses in tissue engineering.

Cellular uptake and cytotoxicity of PEGylated gold nanoparticles in C33A cervical cancer cells

Gold nanoparticles (GNPs) have served as an excellent candidate for biomedical applications. GNPs can be conjugated with carboxyl-polyethylene glycol-thiol (PEG) as a stealth coating which prolongs circulation time [Lipka J et al 2010 Biodistribution of PEG-modified gold nanoparticles following intratracheal instillation and intravenous injection. Biomaterials, 31 , 6574–6581, Janát-Amsbury M et al 2011 Geometry and surface characteristics of gold nanoparticles influence their biodistribution and uptake by macrophages. Eur. J. Pharm. Biopharm, 77 , 417–423] and increases cellular uptake.[He B et al 2017 Increased cellular uptake of peptide-modified PEGylated gold nanoparticles. Biochem. Biophys. Res. Commun., 494 , 339–345, Soenen S. J et al 2014 , The cellular interactions of PEGylated gold nanoparticles: effect of PEGylation on cellular uptake and cytotoxicity. Part. Part. Syst. Charact., 31 , 794–800, Guo J et al 2016 Bioconjugated gold nanoparticles enhance cellular uptake: A proof of concept study for siRNA delivery in prostate cancer cells. Int. J. Pharm., 509 , 16–27. Brandenberger C et al 2010 Quantitative evaluation of cellular uptake and trafficking of plain and polyethylene glycol‐coated gold nanoparticles. Small, 6 , 1669–1678. To examine the biological effects of PEG-coated GNPs, we investigated their cytotoxicity on human cervical cancer C33A cells as compared to citrate-capped GNPs. Our results indicated that PEGylated GNPs markedly induce apoptosis and necrosis causing cell shrinkage and cell membrane asymmetry. 30 nm citrate-capped GNPs were synthesized in aqueous solution using a citrate-reduction method. GNPs were functionalized with PEG (MW = 7500 g mol−1. The GNPs were characterized using scanning electron microscopy (SEM), confirming that the as-synthesized GNPs have a diameter of 30 nm. Dynamic light scattering (DLS) determined that the hydrodynamic diameter of PEGylated GNPs was 78.82 nm, and that of citrate-capped GNPs was 43.82 nm. Zeta potential measurements showed an increase in colloidal stability for PEGylated GNPs as compared to citrate GNPs, with a zeta potential of −33.33 mV observed for citrate-capped GNPs and a zeta potential of −43.38 mV observed for PEGylated GNPs. The PEGylated GNPs were found to effectively induce early and late-stage apoptosis in C33A cells with a significant reduction in total cell viability of 32.3%. Based on the apoptotic activity in C33A cells, PEGylated GNPs may serve as a promising radiosensitizer for cancer treatments.

Triptorelin-functionalized PEG-coated biosynthesized gold nanoparticles: Effects of receptor-ligand interactions on adhesion to triple negative breast cancer cells.

This paper presents the results of an experimental and computational study of the adhesion of triptorelin-conjugated PEG-coated biosynthesized gold nanoparticles (GNP-PEG-TRP) to triple-negative breast cancer (TNBC) cells. The adhesion is studied at the nanoscale using a combination of atomic force microscopy (AFM) experiments and molecular dynamics (MD) simulations. The AFM measurements showed that the triptorelin-functionalized gold nanoparticles (GNP-TRP and GNP-PEG-TRP) have higher adhesion to triple-negative breast cancer cells (TNBC) than non-tumorigenic breast cells. The increased adhesion of GNP-TRP and GNP-PEG-TRP to TNBC is also attributed to the overexpression of LHRH receptors on the surfaces of both TNBC. Finally, the molecular dynamics model reveals insights into the effects of receptor density, molecular configuration, and receptor-ligand docking characteristics on the interactions of triptorelin-functionalized PEG-coated gold nanoparticles with TNBC. A three to nine-fold increase in the adhesion is predicted between triptorelin-functionalized PEG-coated gold nanoparticles and TNBC cells. The implications of the results are then discussed for the specific targeting of TNBC.

Percutaneous ultrasound guided PEG-coated gold nanoparticles enhanced radiofrequency ablation in liver

To investigate the effects of PEG-coated gold nanoparticles on ablation zone volumes following in vivo radiofrequency ablation of porcine liver. This prospective study was performed following institutional animal care and committee approval was used. Radiofrequency ablations were performed in the livers of ten Sus scrofa domesticus swines. During each ablation, 10 mL (mL) of Peg-coated gold nanoparticles at two different concentrations (0.5 mg/mL and 0.01 mg/mL) were injected through the electrode channel into the target zone. For the control group, 10 mL of physiological saline was used. Five to ten minutes after each ablation, contrast enhanced ultrasound (CEUS) was performed to evaluate the volume of the coagulation zone. On day five we performed another CEUS and the animals were sacrificed. Treated tissues were explanted for quantification of the ablation zones’ volumes. Hematoxylin and eosin (H&E) staining was also performed for histologic analysis. A total of 30 ablations were performed in the livers. The mean coagulation zone volume as measured by CEUS on day 5 after RFA was: 21.69 ± 3.39 cm3, 19.22 ± 5.77 cm3, and 8.80 ± 3.33 cm3 for N1, N2 and PS respectively. The coagulation zone volume after N1 and N2 treatments was significantly higher compared to PS treatment (p < 0.001 and p = 0.025 respectively). There was no difference between N1 and N2 treatment (p = 0.60). In our proof-of concept, pilot study we have shown for the first time that when injected directly into the target tissue during RFA, gold nanoparticles can substantially increase the coagulation zone.

SAT502 - In vivo performance of PEG-coated gold nanoparticles mediated ultrasound guided radiofrequency ablation: a pilot study in swine

SAT502 - In vivo performance of PEG-coated gold nanoparticles mediated ultrasound guided radiofrequency ablation: a pilot study in swine

Gold Nanoparticles for Targeting the Fibrotic Heart: A Probe Indicating Vascular Permeability.

Excessive β-adrenergic stimulation induces cardiac fibrosis and inflammation and eventually leads to heart failure. It remains unclear whether the inflammatory factor and infiltration of macrophages are initiated from cardiac cells or the vascular system. We used 13-nm polyethylene glycol (PEG)-coated gold nanoparticles (GNPs) as size probes because they cannot penetrate normal vascular walls, and we found that over-stimulation of β-adrenoceptors mediates cardiac inflammation and fibrosis by increasing vascular permeability. Stimulation with isoproterenol (ISO, a β-adrenoceptor agonist) induced tissue-specific inflammatory infiltration and fibrosis in the hearts of mice. Consistent with these findings, 13-nm PEG-coated GNP as size probes were also observed to have tissue-specific targeting of the fibrotic heart, indicating over-stimulation of β-adrenoceptors, increased vascular permeability in the heart, and initiated cardiac inflammation and fibrosis.

Effect of naked and PEG-coated gold nanoparticles on histopathology and cytokines expression in rat liver and kidneys.

Aim: To compare the effects of 5- and 50-nm naked and PEG-coated gold nanoparticles (AuNP) on proinflammatory cytokines (IL-1β, IL-6, TNF-α) expression and histopathological changes in liver and kidneys of rats. Materials & methods: Rats were injected with different nanoparticles and sacrificed after 24h. Results: Both 5- and 50-nm AuNPs, and 50-nm PEG-AuNPs caused granular clumping of cytoplasm, edema and hydropic dystrophy in hepatic cells. Naked AuNPs of both sizes caused mild shrinkage, whereas 50-nm PEG-AuNPs enlarged the Bowman's space and capsule. Larger nanoparticles produced more profound mRNA expression of cytokines in both the organs. Conclusion: These findings suggest the roles of particle size and coating on immunological response and histopathological changes.

Intracisternal delivery of PEG-coated gold nanoparticles results in high brain penetrance and long-lasting stability

BackgroundThe increasing use of gold nanoparticles (AuNPs) in the field of neuroscience instilled hope for their rapid translation to the clinical practice. AuNPs can be engineered to carry therapeutics or diagnostics in the diseased brain, possibly providing greater cell specificity and low toxicity. Although there is a general enthusiasm for these tools, we are in early stages of their development. Overall, their brain penetrance, stability and cell specificity are critical issues that must be addressed to drive AuNPs to the clinic.ResultsWe studied the kinetic, distribution and stability of PEG-coated AuNPs in mice receiving a single injection into the cisterna magna of the 4th ventricle. AuNPs were conjugated with the fluorescent tag Cy5.5 (Cy5.5-AuNPs) to track their in vivo distribution. Fluorescence levels from such particles were detected in mice for weeks. In situ analysis of brains by immunofluorescence and electron microscopy revealed that Cy5.5-AuNPs penetrated the brain parenchyma, spreading in the CNS parenchyma beneath the 4th ventricle. Cy5.5-AuNPs were preferentially found in neurons, although a subset of resting microglia also entrapped these particles.ConclusionsOur results suggest that the ICM route for delivering gold particles allows the targeting of neurons. This approach might be pursued to carry therapeutics or diagnostics inside a diseased brain with a surgical procedure that is largely used in gene therapy approaches. Furthermore, this approach could be used for radiotherapy, enhancing the agent’s efficacy to kill brain cancer cells.

Gold Nanoparticles Conjugated with Glycopeptides for Lectin Detection and Imaging on Cell Surface.

Lectins are carbohydrate binding proteins and related to various biological events and diseases including virus infection and cancer metastasis. In particular, galactose-binding lectins have attracted attention as targets for drug delivery and cancer markers. We, previously, demonstrated that sugar-modified peptides (glycopeptides) were useful ligands for the detection and characterization of lectins compared to the sugar unit alone. Gold nanoparticles (GNPs) conjugated with mannose-modified glycopeptides were useful in detection of concanavalin A, a mannose binding lectin. The main objective of this study was to expand our glycopeptide-GNP conjugates for detection and imaging of galactose-binding lectins. Four galactose-modified peptides (glycopeptides) were synthesized by Fmoc-based solid peptide synthesis method. Synthesized glycopeptides were conjugated with PEG-coated GNPs using thiol-maleimide chemistry. The interaction between glycopeptide-GNPs (GP/GNPs) (0.5 nM) and RCA120, a galactose binding lectin, (0.5-1000 nM) was evaluated by mesuring absorption spectra of GNPs. The inhibition experiment in the interaction between GP/GNPs (0.5 nM) and RCA120 (100 nM) was performed in the presence of 60 mM α- methyl mannose or 60 mM lactose. HepG2 and MCF7 cells were placed on 22×22 mm cover slip in 6 well cell culture plates (2×105 cells / well) and cultured overnight at 37°C under 5% CO2 condition. 1 mL of GP/GNPs (0.2 nM) were added in each well and incubated for 18 h at 37°C under 5% CO2 condition. After incubation, cells were washed twice with PBS and fixed with 4% paraformaldehyde solution. The cover slips were coated with 90% glycerol and sealed to slide glass. Dark-field images based on elastic light scattering were taken using a Nikon microscope (TieU) with an immersion dark field condenser. In the titration experiment of RCA120, GP/GNPs showed a decrease of absorbance according to the addition of RCA120, suggesting that the aggregation of GP/GNPs is induced through the binding to RCA120. The EC50 values of AA(Gal)/GNP, WF(Gal)/GNP, TS(Gal)/GNP and ED(Gal)/ GNP were estimated as 66.2 nM, 43.2 nM, 38.6 nM and 104.4 nM, respectively. TS(Gal)/GNP showed the lowest EC50 value among GP/GNPs. RCA120 has several binding sites for the galactose, and there are hydrophilic amino acids (Thr24, Glu26, Gln35, Asn42 and Asp44) around one of galactose binding sites. This result indicates that the hydrogen bonds between these amino acids and Thr/Ser residues of TS(Gal) contribute to the efficient aggregation of TS(Gal)/GNP. Next, inhibition experiments in the aggregation of WF(Gal)/GNP with RCA120 revealed that lactose inhibits the WF(Gal)/GNP binding with RCA120, but α-methyl mannose does not, and that WF(Gal)/GNP selectively interacts with RCA120 and forms the aggregate. Finally, a galactose binding protein on the surface of HepG2 cells was successfully visualized by using GP/GNPs as optical probes. Our results demonstrated that GP/GNPs could detect RCA120 by the selective binding and the aggregation formation. Furthermore, a galactose binding protein on the surface of HepG2 cells is successfully visualized using WF(Gal)/GNP as an optical probe. Thus, GNPs conjugated with glycopeptides will be useful probes for the selective detection and imaging of lectins.

Cytotoxicity Study of Gold Nanoparticles on the Basal-Like Triple-Negative HCC-1937 Breast Cancer Cell Line

The Triple Negative “Basal-like” breast cancer (TNBL) tumours have a high proliferative capacity and develop a resistance phenotype associated with metastases. However, the management of TNBL carcinomas is still not standardized. Among the promising trails, gold nanoparticles could be a relevant tool for the development of a targeted treatment for this breast cancer subtype in monotherapy, associated and/or conjugated with other drugs. In this work, we report the cytotoxicity impact of gold nanoparticles wrapped in Poly-Ethylene Glycol (PEG) on the TNBL HCC-1937 breast cancer cell line. PEG-coated gold nanoparticles (PEG-Au NPs) were synthesized by a two-step method using a reduction process followed by a post-functionalization called PEGylation. PEG-Au NPs were characterized using transmission electron microscopy and X-ray diffraction. The gold content of the samples was determined using atomic absorption spectrometer. The cytotoxicity tests were performed using Sulforhodamine B survival test and resazurin viability test. PEG-Au NPs impact analysis on HCC1937 TNBL cell line showed a clear toxic action of type dose dependent and at long term. These PEGylated gold nanoparticles present a promising tool for the development of tumor-specific radiosensitizing vectors, with or without the association of other treatment strategies.

Enhanced Radiation Therapy of Gold Nanoparticles in Liver Cancer

Gold nanoparticles (GNPs) were widely used in X-ray imaging and radiation therapy due to strong photoelectric effects and secondary electrons under high energy irradiation. As liver cancer is one of the most common forms of cancer, the use of GNPs could enhance liver cancer radiotherapy. We synthesized polyethylene glycol (PEG)-coated GNPs of two different sizes by chemical reduction reaction. Blood stability, cellular uptake, cytotoxicity and radiation therapy were investigated. A 3–5 nm red shift of SPR caused by interactions between PEG-coated GNPs and plasma indicated their good stability. Cellular uptake assay showed that PEG-coated GNPs would enhance an appreciable uptake. GNPs preferred to combine with blood proteins, and thus induced the formation of 30–50 nm Au-protein corona. GNPs were endocytosed by cytoplasmic vesicles, localized in intracellular region, and presented concentration dependent cell viability. Clonogenic assay illustrated that the PEG-coated GNPs could sensitize two liver cancer cell lines to irradiation.

Local Effects on Airway Inflammation and Systemic Uptake of 5nm PEG-coated and Uncoated Gold Nanoparticles in Asthmatic Mice

Local Effects on Airway Inflammation and Systemic Uptake of 5nm PEG-coated and Uncoated Gold Nanoparticles in Asthmatic Mice

Low doses of PEG-coated gold nanoparticles sensitize solid tumors to cold plasma by blocking the PI3K/AKT-driven signaling axis to suppress cellular transformation by inhibiting growth and EMT

Metastasis, the primary cause of tumor cell transformation, is often activated during cancer invasion and progression and is associated with poor therapeutic outcomes. The effects of combined treatments that included PEG-coated gold nanoparticles (GNP) and cold plasma on epithelial–mesenchymal transition (EMT) and the maintenance of cancer stem cells (CSC) have not been described so far. Here, we report that co-treatment with GNP and cold plasma inhibited proliferation in cancer cells by abolishing the activation of the PI3K/AKT signaling axis. In addition, co-treatment reversed EMT in solid tumor cells by reducing the secretion of a number of proteins, resulting in the upregulation of epithelial markers such as E-cadherin along with down-regulation of N-Cadherin, Slug and Zeb-1. The inhibition of the PI3K/AKT pathway and the reversal of EMT by co-treatment prevented tumor cells growth in solid tumors. Furthermore, we show that GNP and plasma also suppresses tumor growth by decreasing mesenchymal markers in tumor xenograft mice models. Importantly, co-treatment resulted in a substantial decrease in sphere formation and the self-renewal capacity of glioma-like stem cells. Together, these results indicate a direct link between a decrease of EMT and an increase in cell death in solid tumors following co-treatment with cold plasma and GNP.

Reversible cardiac hypertrophy induced by PEG-coated gold nanoparticles in mice.

Gold nanoparticles (GNPs) are attracting more and more attention for their great potential value in biomedical application. Currently, no study has been reported on the chronic cardiac toxicity of GNPs after repeated administration. Here we carried out a comprehensive evaluation of the chronic cardiac toxicity of GNPs to the heart. Polyethylene glycol (PEG) -coated GNPs at three different sizes (10, 30 and 50 nm) or PBS was administrated to mice via tail vein for 14 consecutive days. Then the mice were euthanized at 2 weeks, 4 weeks or 12 weeks after the first injection. The accumulation of GNPs in the mouse heart and their effects on cardiac function, structure, fibrosis and inflammation were analysized. GNPs with smaller size showed higher accumulation and faster elimination. None of the three sizes of GNPs affected cardiac systolic function. The LVIDd (left ventricular end-diastolicinner-dimension), LVMass (left ventricular mass) and HW/BW (heart weight/body weight) were significantly increased in the mice receiving 10 nm PEG-GNPs for 2 weeks, but not for 4 weeks or 12 weeks. These results indicated that the accumulation of small size GNPs can induce reversible cardiac hypertrophy. Our results provide the basis for the further biomedical applications of GNPs in cardiac diseases.

Abstract 2715: Hepatotoxicity and oxidative stress biomarker study of peg-coated and non-coated gold nanoparticles in Sprague-Dawley rats

Abstract Nanoparticles (NPs) offer a great possibility for biomedical application, not only to deliver pharmaceutics, but also to be used as novel diagnostic and therapeutic approaches. Currently, there are no data available regarding to what extent the degree of the toxicity and the accumulation of gold nanoparticles (GNPs) are present in in vivo model. The aim of this study was to assess the effects, after oral administration, of poly-ethylene-glycol (PEG) coated and non-coated GNPs on various hepatotoxicity and oxidative stress markers such as alanine (ALT), aspartate aminotransferases and alkaline phosphatase, lipid hydro peroxide (LHP) in the mouse model. Sprague -Dawley rats were exposed to four different concentrations of PEG-coated and non-coated GNPs (12.5, 25, 50 and 100 mg/kg BW) and a control. Samples were collected 24 hours after the last treatment following standard protocols. Exposure to PEG-coated and non-coated GNPs enhanced the activities of serum amino-transferases (ALT/AST), alkaline phosphatases (ALP) and concentration of lipid hydro peroxide compared to control. However, PEG-coated GNPs demonstrated enhanced hepatotoxic effect than non-coated GNPs. The scientific findings reported here suggest that both GNPs have the potential to induce hepatotoxicity in Sprague-Dawley rats through activation of the mechanisms of oxidative stress at a higher level of exposure. However, more studies to clarify the role of encapsulation in the in vivo toxicity of GNPs, are required and parallel comparison is preferred. Keywords: gold nanoparticle (GNP), poly-ethylene-glycol, lipid hydroperoxide, serum aminotransferases, alkaline phosphatases, Sprague-Dawley rats, hepatotoxicity. Citation Format: Anita K. Patlolla, Myeisha Fountain, Paul Tchounwou. Hepatotoxicity and oxidative stress biomarker study of peg-coated and non-coated gold nanoparticles in Sprague-Dawley rats. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2715. doi:10.1158/1538-7445.AM2015-2715

Probing the Surface Hydration of Nonfouling Zwitterionic and PEG Materials in Contact with Proteins.

Zwitterionic polymers and poly(ethylene glycol) (PEG) have been reported as promising nonfouling materials, and strong surface hydration has been proposed as a significant contributor to the nonfouling mechanism. Better understanding of the similarity and difference between these two types of materials in terms of hydration and protein interaction will benefit the design of new and effective nonfouling materials. In this study, sum frequency generation (SFG) vibrational spectroscopy was applied for in situ and real-time assessment of the surface hydration of the sulfobetaine methacrylate (SBMA) and oligo(ethylene glycol) methacrylate (OEGMA) polymer brushes, denoted as pSBMA and pOEGMA, in contact with proteins. Whereas a majority of strongly hydrogen-bonded water was observed at both pSBMA and pOEGMA surfaces, upon contact with proteins, the surface hydration of pSBMA remained unaffected, but the water ordering at the pOEGMA surface was disturbed. The effects of free sulfobetaine, free PEG chains with two different molecular weights, and PEG coated gold nanoparticles on the surface hydration of proteins were investigated. The results indicated that free sulfobetaine could strengthen the protein hydration layer, but free PEG chains greatly disrupt the protein hydration layer and likely directly interact with the protein molecules. In contrast to free PEG, the PEG chains anchored on the nanoparticles behave similarly to the pOEGMA surface and could induce strong hydrogen bonding of the water molecules at the protein surfaces.

Oral absorption of PEG-coated versus uncoated gold nanospheres: does agglomeration matter?

BackgroundParticle size is thought to be a critical factor affecting the bioavailability of nanoparticles following oral exposure. Nearly all studies of nanoparticle bioavailability focus on characterization of the primary particle size of the material as supplied or as dosed, and not on agglomeration behavior within the gastrointestinal tract, which is presumably most relevant for absorption.MethodsIn the study reported here, snapshots of agglomeration behavior of gold nanospheres were evaluated in vivo throughout the gastrointestinal tract using transmission electron microscopy. Agglomeration state within the gastrointestinal tract was then used to help explain differences in gastrointestinal particle absorption, as indicated by tissue levels of gold detected using inductively coupled plasma mass spectrometry. Mice were dosed (10 mg/kg) with either 23 nm PEG-coated or uncoated gold nanospheres.ResultsTransmission electron microscopy demonstrates that PEG-coated gold nanoparticles can be observed as primary, un-agglomerated particles throughout the gastrointestinal tract and feces of dosed animals. In contrast, uncoated gold nanoparticles were observed to form agglomerates of several hundred nanometers in all tissues and feces. Inductively coupled plasma mass spectrometry shows significantly higher levels of gold in tissues from animals dosed with PEG-coated versus uncoated 23 nm gold nanoparticles. Retention of particles after a single oral gavage was also very high, with all tissues of animals dosed with PEG-coated particles having detectable levels of gold at 30 days following exposure.ConclusionsQualitative observation of these particles in vivo shows that dispersed PEG-coated particles are able to reach the absorptive tissues of the intestine while agglomerated uncoated particles are sequestered in the lumen of these tissues. However, the large differences observed for in vivo agglomeration behavior were not reflected in oral absorption, as indicated by gold tissue levels. Additional factors, such as surface chemistry, may have played a more important role than in vivo particle size and should be investigated further.

Abstract 2284: Cytotoxic and genotoxic effects of PEG-coated gold nanoparticles in HK-2 cells

Abstract Biomolecular functionalization of gold nanoparticles (GNP's) have led to a dramatic expansion of their potential biomedical applications, including biosensorics, bioimaging, photothermal therapy, and targeted drug delivery. As the range of gold nanoparticle types and their applications continues to increase, human safety concerns are gaining attention, which makes it necessary to better understand the potential toxicity hazards of these novel materials. The main objective of this study was to determine the cytotoxic and genotoxic potential of poly-ethylene-glycol-coated gold nanoparticles (PEG-GNPs) in HK-2 cells. These cells were grown under sterile conditions in 96-well plate until 80% confluency. Four exposure concentrations (125, 250, 500 and 1000 µg/ml) of PEG-coated GNP's and a control were used. Following exposure to PEG-coated GNP's, cytotoxicity assay (MTS) was performed for 24 and 48 hrs using standard protocol. Genotoxic effects of GNP's were determined measuring DNA damage using comet assay. The results demonstrated a dose and time dependent decrease in cell viability with PEG-coated GNPs and an increase in percent DNA damage in exposed cells compared to control. The difference in the cytotoxic effect between 24 and 48 hrs was not statistically significant however, the genotoxic effect was statistically significant both in time and dose. The cellular findings reported here do suggest that GNPs has the potential to induce cell death and cause damage to DNA in HK-2 cells. However, more studies to clarify the role of encapsulation in the in vitro toxicity of GNP's, are required and parallel comparison is preferred. Note: This abstract was not presented at the meeting. Citation Format: Anita K. Patlolla, Tammy Epting, Lisabeth Thrasher, Paul B. Tchounwou. Cytotoxic and genotoxic effects of PEG-coated gold nanoparticles in HK-2 cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2284. doi:10.1158/1538-7445.AM2014-2284

Raman Scattering Enhancement of Peg Coated Gold Nanoparticles of Defined Size

In this work a surface-enhanced Raman scattering (SERS) study was carried out, in order to determine the dependence of crystal violet (CV) SERS intensity on the size of gold nanoparticles (GNPs) synthesized by reduction with polyethylene glycol (PEG), with molar masses 200 and 10000. By using UV-Vis spectroscopy and transmission electron microscopy (TEM), the size of the synthesized nanoparticles, in the range of 7–60 nm, showing spherical and polygonal geometries, was determined. Zeta potential measurements were performed in order to assess the stability of the gold colloids. The SERS spectra of different concentrations of CV analyte, using 7 to 60 nm diameter PEG-coated GNPs, were recorded to determine the optimal size of the nanoparticles that provides the highest SERS intensity. This study confi rms that the intensity of the SERS signal increases with increase in the diameter of the GNPs.