Doses Of AuNPs Research Articles

Biocompatible cellulose nanocrystal-based Trojan horse enables targeted delivery of nano-Au radiosensitizers to triple negative breast cancer cells.

A hybrid cellulose-based programmable nanoplatform for applications in precision radiation oncology is described. Here, sugar heads work as tumor targeting moieties and steer the precise delivery of radiosensitizers, i.e. gold nanoparticles (AuNPs) into triple negative breast cancer (TNBC) cells. This "Trojan horse" approach promotes a specific and massive accumulation of radiosensitizers in TNBC cells, thus avoiding the fast turnover of small-sized AuNPs and the need for high doses of AuNPs for treatment. Application of X-rays resulted in a significant increase of the therapeutic effect while delivering the same dose, showing the possibility to use roughly half dose of X-rays to obtain the same radiotoxicity effect. These data suggest that this hybrid nanoplatform acts as a promising tool for applications in enhancing cancer radiotherapy effects with lower doses of X-rays.

Physiologically-Based Kinetic Modeling of Intravenously Administered Gold (Au) Nanoparticles.

Physiologically-based kinetic (PBK) modeling is a valuable tool to understand the kinetics of nanoparticles (NPs) in vivo. However, estimating PBK parameters remains challenging and commonly requires animal studies. To develop predictive models to estimate PBK parameter values based on NP characteristics, a database containing PBK parameter values and corresponding NP characteristics is needed. As a first step toward this objective, this study estimates PBK parameters for gold NPs (AuNPs) and provides a comparison of two different NPs. Two animal experiments are conducted in which varying doses of AuNPs attached with polyethylene glycol (PEG) are administered intravenously to rats. The resulting Au concentrations are used to estimate PBK model parameters. The parameters are compared with PBK parameters previously estimated for poly(alkyl cyanoacrylate) NPs loaded with cabazitaxel and for LipImage 815. This study shows that a small initial database of PBK parameters collected for three NPs is already sufficient to formulate new hypotheses on NP characteristics that may be predictive of PBK parameter values. Further research should focus on developing a larger database and on developing quantitative models to predict PBK parameter values.

Neuroprotective Effect of Gold Nanoparticles and Alpha-Lipoic Acid Mixture against Radiation-Induced Brain Damage in Rats

The current study aims to evaluate the possible neuroprotective impact of gold nanoparticles (AuNPs) and an alpha-lipoic acid (ALA) mixture against brain damage in irradiated rats. AuNPs were synthesized and characterized using different techniques. Then, a preliminary investigation was carried out to determine the neuroprotective dose of AuNPs, where three single doses (500, 1000, and 1500 µg/kg) were orally administrated to male Wistar rats, one hour before being exposed to a single dose of 7Gy gamma radiation. One day following irradiation, the estimation of oxidative stress biomarkers (malondialdehyde, MDA; glutathione peroxidase, GPX), DNA fragmentation, and histopathological alterations were performed in brain cortical and hippocampal tissues in both normal and irradiated rats. The chosen neuroprotective dose of AuNPs (1000 µg/kg) was processed with ALA (100 mg/kg) to prepare the AuNPs-ALA mixture. The acute neuroprotective effect of AuNPs-ALA in irradiated rats was determined against valproic acid as a neuroprotective centrally acting reference drug. All drugs were orally administered one hour before the 7Gy-gamma irradiation. One day following irradiation, animals were sacrificed and exposed to examinations such as those of the preliminary experiment. Administration of AuNPs, ALA, and AuNPs-ALA mixture before irradiation significantly attenuated the radiation-induced oxidative stress through amelioration of MDA content and GPX activity along with alleviating DNA fragmentation and histopathological changes in both cortical and hippocampal tissues. Notably, the AuNPs-ALA mixture showed superior effect compared to that of AuNPs or ALA alone, as it mitigated oxidative stress, DNA damage, and histopathological injury collectively. Administration of AuNPs-ALA resulted in normalized MDA content, increased GPX activity, restored DNA content in the cortex and hippocampus besides only mild histopathological changes. The present data suggest that the AuNPs-ALA mixture may be considered a potential candidate for alleviating radiation-associated brain toxicity.

Nephroprotective Effect of Green Synthesised Gold Nanoparticles Using Bark Extract of Terminalia arjuna on Acetaminophen Induced Nephrotoxicity in Male Albino Rat

Green synthesised gold nanoparticles offer a great promise in biomedicine. An overdose of acetaminophen causes severe hepatotoxicity and nephrotoxicity. The development of nephroprotective drugs through eco-friendly production routes is a major challenge for current pharmacology. This study was undertaken to examine the therapeutic effects of green synthesised gold nanoparticles (AuNPs) using aqueous bark extract of Terminalia arjuna, on acetaminophen induced nephrotoxicity in male albino rats and also to select the most effective dose of AuNPs to protect from nephrotoxicity . Terminalia arjuna , is a herbal plant of high interest in Asian traditional medicine. The bark of this tree has been widely used in the preparation of ayurvedic formulations such as powerful cardiotonic, antioxidative, antiuremic and antimicrobial properties. In this study 36 experimental albino rats were taken and randomly divided into 6 groups. Group 1 served as normal control, Group 2 received acetaminophen intraperitoneally at concentration of 500mg /kg of body weight for 14 days and Groups 3,4,5,6 were co-administered with acetaminophen (500mg/kg/day) along with AuNPs at doses 55, 175, 550, 2000 µg/kg/day intraperitoneally for 14 days. After 14 days all animals were sacrificed for biochemical and histopathological studies. Among different experimental doses of AuNPs (55,175,550, 2000µg/kg/day), 175µg/kg/day showed more potent activity towards biochemical indices and histopathological studies. There was significant (p<0.05) increase in Urea, Creatinine, CRP and MDA levels but significant decrease in SOD, CAT and GSH activity in acetaminophen treated group, in comparison to control group but co-administration with AuNPs (175µg/kg/day) restored the activities of these biochemical markers and also of the antioxidant enzymes. Hence,this study confirmed that AuNPs at dose 175µg/kg/day have better nephroprotective efficacy.

Discriminatory alteration of carbohydrate homeostasis by gold nanoparticles ingestion in Drosophila.

With the extensive usage of gold nanoparticles (AuNPs) in various industrial sectors and biomedical applications, evaluation of their possible effects on human health becomes imperative. Therefore, the present study was aimed toward assessing the dose-dependent impact of AuNPs ingestion on metabolic homeostasis using Drosophila melanogaster as a model system. We found that larval ingestion of higher dose of AuNPs significantly reduced body weight. Further analysis of the crucial energy reservoir showed selective alteration in carbohydrate levels without any change in the lipid and protein levels. Transcriptional downregulation of glycogen synthase further supported impaired glycogen metabolism in flies supplemented with higher dose of AuNPs. Additionally, ingestion of higher dose of AuNPs in larvae results in significantly increased levels of reactive oxygen species (ROS) in the peripheral tissues, suggestive of stress condition. Our findings clearly imply that supplementing higher doses of AuNPs at an early developmental stage can potentially cause weight loss, impair glycogen metabolism, and elevate ROS production. Therefore, determination of a biologically effective dose is critical for the safety of mankind and vulnerable populations at the workplace.

Effective Dose of Herbal Gold Nanoparticles for Protection of Acetaminophen-Induced Hepatotoxicity in Male Albino Rats

Overdose of acetaminophen causes hepatotoxicity due to NAPQI formation. The green synthesis of gold nanoparticles represents as a novel drug carrier in the field of drug delivery system. This study was designed to investigate the protective effect of green synthesized herbal gold nanoparticles (AuNPs) using the aqueous bark extract of Terminalia arjuna against acetaminophen-induced hepatotoxicity in an experimental rat model. In this study, group 1 served as normal control; group 2 received acetaminophen intraperitoneally at a concentration of 500 mg/kg of body weight for 14 days; and groups 3, 4, 5, and 6 were co-administered with acetaminophen (500 mg/kg/day) and AuNPs (55, 175, 550, 2000 μg/kg/day) intraperitoneally for 14 days. After 14 days, all animals were sacrificed for biochemical and histopathological studies. Among different experimental doses of AuNPs (55, 175, 550, 2000 μg/kg/day), dose 175 μg/kg/day showed more potent activity towards wellness parameters, biochemical indices, and histopathological studies. There was a significant (p < 0.05) increase in SGOT, SGPT, ALP, bilirubin, and MDA levels, but a significant decrease in SOD, CAT, and GSH activities in the hepatotoxic group in comparison with the control group, but co-administration with AuNPs (175 μg/kg/day) restored the activities of these biochemical markers. Hence, this study confirmed that AuNPs at a dose 175 μg/kg/day has better hepatoprotective efficacy.

The Potential Impacts of Gold Nanoparticles on the Mucous Membrane of the Albino Rats' Tongues

Abstract Introduction: With the growing interest in the applications of gold nanoparticles (AuNPs) in biotechnology and their physiological effects, possible toxicity of gold nanoparticles is becoming an increasingly important issue. It was shown that the toxicity is both dose- and size-dependent, and the AuNPs of higher concentration would cause more cytotoxicity. Objectives: The aim of this work was to study the toxic effect of intraperitoneal administration of gold nanoparticles -if any- on the mucous membrane of the tongues of albino rats and the possibility of one-month recovery period. Material and methods: Forty-six male albino rats were used in the present investigation. They were divided into the following groups: Group (1) (16 rats) served as controls, they received the solvent of AuNPs intraperitoneally daily for 21 days. Group (2) (15 rats) received 10mg/kg body weight of AuNP solution intraperitoneally daily for 21 days. Group (3) (15 rats) were treated the same way as Group 2 for 21 days and then left for one-month as a recovery period. Results: Examination of the tongue of the rats which were exposed to gold nanoparticles solution revealed atrophic and degenerative changes of both the dorsal and ventral surfaces of the tongue as well as the lingual salivary glands. The examined tongues of the rats which were allowed a recovery period showed improvement in the histological picture. Conclusion: Exposure to over dose of AuNPs causes atrophic and degenerative changes. A recovery period of one-month can lead to regeneration and improvement in the histological picture.

Network-based analysis implies critical roles of microRNAs in the long-term cellular responses to gold nanoparticles.

Since gold nanoparticles (AuNPs) have great potential to bring improvements to the biomedical field, their impact on biological systems should be better understood, particularly over the long term, using realistic doses of exposure. MicroRNAs (miRNAs) are small noncoding RNAs that play key roles in the regulation of biological pathways, from development to cellular stress responses. In this study, we performed genome-wide miRNA expression profiling in primary human dermal fibroblasts 20 weeks after chronic and acute (non-chronic) treatments to four AuNPs with different shapes and surface chemistries at a low dose. The exposure condition and AuNP surface chemistry had a significant impact on the modulation of miRNA levels. In addition, a network-based analysis was employed to provide a more complex, systems-level perspective of the miRNA expression changes. In response to the stress caused by AuNPs, miRNA co-expression networks perturbed in cells under non-chronic exposure to AuNPs were enriched for target genes implicated in the suppression of proliferative pathways, possibly in attempt to restore cell homeostasis, while changes in miRNA co-expression networks enriched for target genes related to activation of proliferative and suppression of apoptotic pathways were observed in cells chronically exposed to one specific type of AuNPs. In this case, miRNA dysregulation might be contributing to enforce a new cell phenotype during stress. Our findings suggest that miRNAs exert critical roles in the cellular responses to the stress provoked by a low dose of NPs in the long term and provide a fertile ground for further targeted experimental studies.

Investigating the effect of gold nanoparticles on hydatid cyst protoscolices under low-power green laser irradiation.

Various scolicidal agents are applied for the destruction of protoscolices in cysts media. Undesirable complications of the scolicidal agents limit the techniques to treat the cyst disease. Therefore, new non-toxic scolicidal agents are needed. Upon laser light irradiation, the photothermal gold nanoparticles (AuNPs) convert the absorbed laser light into heat through photothermal effect which kills the surrounding protoscolices by rising the temperature of the cysts media. In this study, we introduced biocompatible AuNPs as a non-toxic scolicidal agent to cure liver hydatid cysts. The protoscoleces were collected from the livers of naturally infected sheeps. In each experimental group, 1.5 mL suspensions of hydatid liquid containing protoscolices were added to test tubes. The test tubes were divided into five groups. Control, AuNPs only, Green laser only, High-dose AuNPs + laser and Low-dose AuNPs + laser groups. Two concentrations (0.4 and 0.8 mL) of AuNPs and three laser powers (30, 50, 150 mW) were applied for 30, 60 and 120 minutes to the groups. Then the ciysts liquid assessed under a light microscope and determined the viability of protoscoleces. Protoscolices in high-dose AuNPs group were destructed up to 89.30% deaths under 150 mW laser power for 120 minutes. However, negligible cell deaths were observed in cases where only AuNPs added or only laser irradiated groups. Increasing the dose of AuNPs or laser power or duration of aplication increased the protoscolosidal death rate. In the study, we have successfully demonstrated that the AuNPs are an effective therapeutic and scolicidal agent to cure hydatid cyst disease under laser irradiation.

Impact of citrate- and chitosan-capped gold nanoparticles on the liver of Swiss albino mice: Histological and cyto-genotoxic study

The present study aimed to disclose the histological alterations and cyto-genotoxic potential induced by citrate- and chitosan-capped AuNPs on liver of adult Swiss albino mice. Animals were randomly divided into 8 groups. The first two groups were intraperitoneally (i.p) injected with physiological saline once and left for 10 days and every other day for 21 days, respectively, and kept as negative control groups. While the third and fourth groups were injected i.p with a single dose of 2 mg/kg of citrate- and chitosan-capped AuNPs, respectively, and left for 10 days. The fifth and sixth groups were injected i.p every other day for 21 days with 200 µg/kg of citrate- and chitosan-capped AuNPs, respectively. Animals of the seventh and eighth groups were injected i.p with 50 mg/kg cyclophosphamide once and left for 10 days and with 20 mg/kg cyclophosphamide every other day for 21 days, respectively. The livers of mice were dissected and processed for microscopic examination and for analyzing the expression of inflammation-related genes using RT-PCR. In addition, bone marrow samples were taken to investigate the mitotic index and the chromosomal aberrations. The present study showed various degrees of structural changes in the liver of animals received AuNPs. Such changes were more prominent in animals treated with a single dose of AuNPs, particularly with citrate-capped AuNPs as compared to chitosan-capped AuNPs. Furthermore, genotoxic analysis did not reveal any genotoxicity for AuNPs with both coats. Therefore, chitosan-capped AuNPs were less hepatotoxic than citrate-capped ones. However, it has not been proven that AuNPs are genotoxic by both coats.

Redox Status, Hematological Parameters as Well Liver and Kidney Function Indicators in Blood of Chickens Receiving Gold Nanoparticles

Abstract The aim of the study was to assess the biocompatibility of gold nanoparticles (Au-NPs) for chickens by investigating their effect on their growth, hematological parameters, markers of oxidative stress, and indicators of liver and kidney function. The experiment was carried out on 54 chickens assigned to 3 experimental groups of 18 birds each. The control group did not receive gold nanoparticles. The birds in group Au-NPs2.0 received gold nanoparticles in a tube into a crop at a rate of 2.0 mg/kg body weight/day, while the birds in AuNPs5.0 group at a rate of 5.0 mg/kg body weight/day. The blood for analysis was collected after 7, 14, 21 and 28 days of Au-NPs application. The obtained results indicate that short-term (7–14 day) exposure to lower dose (2.0 mg/kg b.w./day) of AuNPs had no toxic impact on chickens, but the extension of the duration time caused toxicological effects evidenced by growth inhibition as well as induction of oxidative stress and liver injury. The higher dose of AuNPs (5.0 mg/kg b.w./day) exerted toxic effects already after 7–14 days of supplementation.

Promising therapeutic effect of gold nanoparticles against dinitrobenzene sulfonic acid-induced colitis in rats.

Aim: The aim of this study is to evaluate the therapeutic effect of two different doses of naked gold nanoparticles (AuNPs) in the experimental colitis in rats. Materials & methods: Colitis was induced in rats by single intracolonic instillation of dinitro-benzene sulfonic acid (250μl DNBS-25mg/rat). 4 days later the rats were intravenously injected with a single dose of AuNPs 40 and 400μg/kg of size 16-25nm. Results: In comparison with dinitro-benzene sulfonic acid-colitis group, the exposure to AuNPs for 72 h ameliorated the liver and kidney functions, increased the regenerative capacity of damaged colon tissues, suppressed the inflammatory cytokine response and diminished the colonic malondialdehyde and myeloperoxidase activities. In addition, there was a remarkable improvement in the antioxidant defense system. Conclusion: Our study suggested a new therapy for experimental colitis without noticeable drawbacks.

The systematic evaluation of size-dependent toxicity and multi-time biodistribution of gold nanoparticles.

As a promising nanomaterial, gold nanoparticles (Au NPs) have been widely applied in diagnosis, drug and gene delivery, and photothermal therapy. However, the toxicity and biodistribution profile of differently sized Au NPs still remains controversial and incomplete, thus hindering their further applications. Herein, a systematic evaluation of size effect on toxicity and multi-time (from 4 h to 90 days) biodistribution of Au NPs ranging from 6.2 nm to 61.2 nm was conducted. The in vitro toxicity by MTT assays manifested that toxicity could be distinctly observed and increased with size decreasing when the dose of Au NPs reached up to a certain amount (1 mM). Subsequently, the corresponding toxicity mechanism was further studied via reactive oxygen species assay kit and the results indicated that Au NPs with various sizes would induce different oxidative stress which was accountable for the ultimate toxicity. Furthermore, the result of the biodistribution showed that Au NPs with larger sizes (42.5 and 61.2 nm) accumulated mainly in liver and spleen while little or none were found in heart, kidney and lung. Dissimilarly, smaller ones (6.2 and 24.3 nm) were distributed not only in liver and spleen but also in other organs. Additionally, most of the Au NPs were excreted out in less than 30 days, whereas there were still bits of remains in liver and spleen up to 90 days, especially for the 42.5 and 61.2 nm Au NPs. These findings are meaningful for the design of the Au NPs in the biomedical fields.

Evaluation of immunotropic activity of gold nanocolloid in chickens

Gold nanoparticles (AuNPs) are one of the most examined nanomaterials, but information about their immunogenic potential is still insufficient. Understanding interaction of AuNPs with immune system is essential in designing their safety and possibilities of biomedical applications. An experiment was conducted to determine immunotropic activity of gold nanocolloid (AuNPs) administered orally to chickens depending on dose and duration time. 162 birds were assigned to 9 experimental groups of 18 birds each. The control group (C) did not receive AuNPs. Groups: T10.5, T11.0, T11.5, T12.0, received nano-gold in a rate of 0.5 mg/kg body weight/d, 1.0 mg/kg body weight/d, 1.5 mg/kg body weight/d and 2.0 mg/kg body weight/d in 8–14, 22–28 and 36–42 days of the life. The birds in groups T20.5, T21.0, T21.5, T22.0, received nano-gold in the same doses, but only in 8–10, 22–24 and 36–38 days of life. Phagocytic activity of leukocytes was determined in vitro using Staphylococcus aureus 209P strain, their respiratory burst activity was quantified by nitroblue tetrazolium reduction test. Serum lysozyme content was determined by the turbidimetric method. The Wintrobe method was used to determine the erythrocyte sedimentation rate. Ceruloplasmin in the blood plasma was estimated by the p-phenylenediamine colorimetric method. The level of chicken immunoglobulins: IgA, IgM and IgY and interleukin IL-6 in the blood were determined using ELISA tests. The lowest dose of AuNPs, independently on duration time had no effect on immune parameters of chickens. In all other groups receiving nano-gold for a shorter period (T2), there was an increase in the respiratory burst activity of leukocytes and a drop in lysozyme activity in blood. The higher doses (1.5 and 2.0 mg/kg body weight/d) of the nano-gold administered for the longer time period had a pro-inflammatory effect, as indicated by an increase in the level of interleukin 6 and ceruloplasmin activity as well as the erythrocyte sedimentation rate. They also contributed to an elevation of class IgA and IgY contents in blood. The results of the study revealed that the influence of nano-gold on immune response of chickens were dependent both on dose and duration time. Long lasting administration of higher doses of AuNPs contributed to adverse effect in form of inflammation response. To avoid the development of inflammatory reaction, administered dose of nano-gold should not exceed 1.0 mg/kg body weight/d.

Gold nanoparticles ameliorate acetaminophen induced hepato-renal injury in rats

Valuable effects of gold particles have been reported and used in complementary medicine for decades. The aim of this study was to evaluate the therapeutic efficacy of gold nanoparticles (AuNPs) against acetaminophen (APAP) induced toxicity. Albino rats were administered APAP at a dose of 2g/kg p.o. once only. After 24h of APAP intoxication, animals were treated with three different doses of AuNPs (50μg/kg, 100μg/kg, 150μg/kg) orally or silymarin at a dose of 50mg/kg p.o., once only. Animals of all the groups were sacrificed after 24h of last treatment. APAP administered group showed a significant rise in the AST, ALT, SALP, LDH, cholesterol, bilirubin, albumin, urea and creatinine in serum which indicated the hepato-renal damage. A significantly enhanced LPO and a depleted level of GSH were observed in APAP intoxicated rats. Declined activities of SOD and Catalase, after acetaminophen exposure indicated oxidative stress in liver and kidney. The activities of ATPase and glucose-6-Phosphatase were significantly inhibited after APAP administration. AuNPs treatment reversed all variables significantly towards normal level and was found nontoxic. Thus it is concluded that gold nanoparticles played a beneficial role in reducing acetaminophen induced toxicity and can be used in the development of drug against hepatic as well as renal diseases, after further preclinical and clinical studies.

Gum-Mediated Fabrication of Eco-Friendly Gold Nanoparticles Promoting Cell Division and Pollen Germination in Plant Cells

In this study we reported a simple approach for the green synthesis of gold nanoparticles (AuNPs) using the Terminalia arjuna gum extract as a source of reducing and stabilizing compounds. The fabrication of AuNPs was confirmed by UV–Vis spectroscopy, XRD and TEM. UV–Vis spectrum clearly showed the absorption peak at 520 nm, which is due to the surface Plasmon resonance on AuNPs. XRD analysis highlighted the crystalline nature of AuNPs, with face-centered cubic structure. TEM showed that spherical shape of nanoparticles, with average particles size of 10–20 nm. AuNPs did not show any inhibitory activity both on Gram-positive and Gram-negative bacteria. Furthermore, different doses of AuNPs (0, 100, 500 and 1000 µM) were tested to assess their potential impact on mitotic division and pollen germination. A treatment with 100 µM of AuNPs significantly induced both mitotic division and pollen germination. In the plant cells, the passive uptake of AuNPs through cytosol allowed them to move towards the nuclear pore complex. Subsequently, they interacted with histone protein leading to mitotic cell division and pollen germination. Overall, our study highlighted the potential of gum-fabricated AuNPs in cytogenetic, gene expression and plant tissue culture applications.

Pancreatic Response to Gold Nanoparticles Includes Decrease of Oxidative Stress and Inflammation In Autistic Diabetic Model

Background: Gold nanoparticles (AuNPs) have a wide range of applications in various fields. This study provides an understanding of the modulatory effects of AuNPs on an antioxidant system in male Wistar diabetic rats with autism spectrum disorder (ASD). Normal littermates fed by control mothers were injected with citrate buffer alone and served as normal, untreated controls controlin this study. Diabetes mellitus (DM) was induced by administering a single intraperitoneal injection of streptozotocin (STZ) (100 mg/kg) to the pups of (ND) diabetic group, which had been fasted overnight. Autistic pups from mothers that had received a single intraperitoneal injection of 600 mg/kg sodium valproate on day 12.5 after conception were randomly divided into 2 groups (n 2 7/group) as follow; administering single intraperitoneal injection of streptozotocin (STZ) ( (100 mg/kg) to the overnight fasted autistic pups of (AD) autistic diabetic group. The treatment was started on the 5th day after STZ injection with the same dose as in group II and it was considered as 1st day of treatment with gold nanoparticles for 7 days to each rat of (group IV) treated autistic diabetic group(TAD) at a dosage of 2.5 mg/kg. b. wt. Results: At this dose of administration AuNPs, the activities of hepatic superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase were greater in group TAD compared with the control group (P < 0.05). Oxidised glutathione levels were lower (P > 0.05) in the liver of autistic diabetic AuNPs -supplemented rats, whereas reduced glutathione was markedly higher than in control rats, especially after administration of AuNPs. Moreover, the kidney functions in addition to the fat profile scoring supported the protective potential of that dose of AuNPs. The beta cells revealed euchromatic nuclei with no evidence of separation of nuclear membrane. Conclusions: Our results showed that AuNPs improved many of the oxidative stress parameters (SOD, GPx and, CAT), plasma antioxidant capacity (ORAC) and lipid profile relative to the other parameters. In addition to the apparent reversibility of the pancreatic B cell in group IV which may reflect the regenerative capacity of AuNPs.

Statistical analysis of gold nanoparticle-induced oxidative stress and apoptosis in myoblast (C2C12) cells

Nanoscale gold particles (Au-NPs) with a diameter below 20nm are notably important candidates for various important applications because of their extraordinary quantum size effects. Their high surface area-to-volume ratio facilitates their very high reactivities; therefore, they can be utilised in different ways in biomedical applications. For example, these nanoparticles can penetrate into cells and bind with proteins or DNA and are therefore potential nanostructures employed for sensing and detecting various biological identities. In the present work, we synthesised Au-NPs via a colloidal process using chloroauric acid (HAuCl4·4H2O) and trisodium citrate dihydrate (N3C6H5O7) as a reducing agent. The shape evolution and the structural properties of these NPs were investigated in detail using TEM and high resolution HR-TEM investigations. Different doses of Au NPs have been applied to treat C2C12 myoblast cells in a 24-h incubation period, and a dose-dependent study has also been performed. The cells were cultivated in DMEM with FBS and antibiotics (strepto-penicillin) at 37°C in a 5% humidified environment of CO2 and 95% air. Cell viability analysis using MTT assays revealed that increased concentration of Au NPs (100–1000ng/mL) resulted in a decreased density of cells. The amount of reactive oxygen species (ROS) in C2C12 cells analysed with Au-NPs (in a dose-dependent manner), and the RT-PCR data demonstrated the up-regulation of caspase-3 and caspase-7 genes in C2C12 cells after treatment with Au-NPs. These results have been confirmed by detailed confocal microscopy (CLSM) studies. In addition, the quantitative analysis of the Au-NPs was also confirmed by statistical analytical parameters, such as precision, accuracy, linearity, limits of detection (LOD) and limit of quantitation (LOQ), quantitative recoveries and relative standard deviation (RSD), and the analyses again exhibited a significant and large effect of Au NPs on C2C12 cells.

Anticancer (in vitro) and antimicrobial effect of gold nanoparticles synthesized using Abelmoschus esculentus (L.) pulp extract via a green route

Green synthesis of gold nanoparticles (Au NPs) using Abelmoschus esculentus (L.) pulp extract has been elaborately studied and reported here. The Au NPs have been characterized using several techniques. Optical analysis indicates adequate stability of the synthesized Au NPs, while FTIR analyses the fact that phytochemicals present in the Abelmoschus esculentus (L.) pulp extract play the key role in stabilizing the Au NPs. Morphological study shows that the nanoparticles are mostly spherical in shape with an average particle size of ∼14 nm, and these results are comparable with the particle size obtained from XRD. The selected area electron diffraction pattern indicates the crystalline nature of the Au NPs, which is further confirmed from XRD studies. The present study also demonstrates the in vitro efficacy of Au NPs against Jurkat cells. Results show that the IC50 dose of Au NPs is capable of significantly elevating intracellular reactive oxygen species and diminishing mitochondrial membrane potential, indicating the effective involvement of apoptosis in cell death. Furthermore, the synthesized Au NPs show a sufficient degree of antimicrobial activity against different types of bacteria. These results clearly show that the Abelmoschus esculentus (L.) pulp synthesized Au NPs have excellent medicinal applications.

Abstract 4449: Deep penetration of PDT drugs into tumors via non-covalent drug-gold nanoparticle conjugates

Abstract In 2010, more than a million new cancer cases are expected to be diagnosed with half resulting in death, at an NIH estimated total yearly cost of $263.8 billion. Therefore, there is a critical need to improve both cancer diagnostics and therapeutics; future theranostics aim to combine both in a single visit. Consequently, efficient delivery of hydrophobic, theranostic drugs is necessary. This study presents a novel non-covalent PDT cancer drug-gold nanoparticle (Au NP) conjugate system that is able to perform rapid drug release deep into tumors within hours rather than days. The drug delivery mechanism of the PDT drug Pc 4 using Au NPs into tumors by passive accumulation was investigated via fluorescence imaging of Pc 4, elemental gold analysis, and histological staining. The pharmacokinetics of the conjugates over a 7 day period showed rapid drug excretion, as monitored via the fluorescence of Pc 4 which decreased significantly to near baseline levels. Moreover, the biodistribution of Au NPs indicated clearance of the conjugates from the mice. The spleen, liver, kidneys, and urinary tract showed accumulation of Au NPs and accounted for 33.6% of the injected dose at only 4 hrs, suggesting possible excretion pathways, since the total injected dose of Au NPs recovered from dissected organs decreased by 33.4%. Histological analysis corroborated these findings; Au NPs in the liver were found in liver sinusoids and hepatocytes, Au NPs in the spleen were found near macrophages, Au NPs in the kidney were located in the glomerulus, and Au NPs in the urinary tract were found in the stroma. At 4 hrs post-injection, ∼76% of the injected dose of Au NPs was recovered in harvested organs, and AuNPs accumulated passively in tumors with an average accumulation of 8 ± 6 % ID (or ∼62.46 μg/g of tumor tissue). The tumor (4 hrs post-injection) showed very high fluorescence intensities further suggesting the passive accumulation of Pc 4 via the Au NPs within the tumor. In vitro studies showed the conjugates delivered 389.4 moles of Pc 4 per mole of Au NP into cells in 4 hrs; in vivo studies showed approximately 10 RFUs (of Pc 4)/ μg of gold delivered into tumor tissues. Ultimately, this study suggests that Pc 4 non-covalently loaded Au NPs that penetrate deep into the tumor interior provide a very attractive approach to delivery cancer drugs to visualize carcinomas and track therapeutic responses. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4449. doi:10.1158/1538-7445.AM2011-4449