Nanomaterials in food and agriculture: An overview on their safety concerns and regulatory issues.

Nanotechnology has seen exponential growth in last decade due to its unique physicochemical properties; however, the risk associated with this emerging technology has withdrawn ample attention in the past decade. Nanotoxicity is majorly contributed to the small size and large surface area of nanomaterials, which allow easy dispersion and invasion of anatomical barriers in human body. Unique physio-chemical properties of nanoparticles make the investigation of their toxic consequences intricate and challenging. This makes it important to have an in-depth knowledge of different mechanisms involved in nanomaterials's action and toxicity. Nano-toxicity has various effects on human health and diseases as they can easily enter into the humans via different routes, mainly respiratory, dermal, and gastrointestinal routes. This also limits the use of nanomaterials as therapeutic and diagnostic tools. This review focuses on the nanomaterial-cell interactions leading to toxicological responses. Different mechanisms involved in nanoparticle-mediated toxicity with the main focus on oxidative stress, genotoxic, and carcinogenic potential has also been discussed. Different methods and techniques used for the characterization of nanomaterials in food and other biological matrices have also been discussed in detail. Nano-toxicity on different organs-with the major focus on the cardiac and respiratory system-have been discussed. Conclusively, the risk management of nanotoxicity is also summarized. This review provides a better understanding of the current scenario of the nanotoxicology, disease progression due to nanomaterials, and their use in the food industry and medical therapeutics. Briefly, the required rules, regulations, and the need of policy makers has been discussed critically.

Involvement of Bcl-2 Activation and G1 Cell Cycle Arrest in Colon Cancer Cells Induced by Titanium Dioxide Nanoparticles Synthesized by Microwave-Assisted Hybrid Approach.

The toxic effect of TiO2 nanoparticles (TNP) greatly varies with the variation in synthesis protocol followed. Any morphological alteration of TNPs affects their activity. In the present study, we report the detailed toxicological analysis of TNPs fabricated by a microwave irradiation-assisted hybrid chemical approach. The toxicological mechanism was studied in human colon cancer cell lines (HCT116). Results indicate that TNP induces oxidative stress on HCT116, which, in turn, causes mitochondrial membrane depolarization. We also observed activation of Bcl-2 and caspase-3 by Western blot analysis. This indicates TNPs induce mitochondrial-mediated apoptosis. Furthermore, G1 cell cycle arrest was observed by flow-cytometric analysis. This study provides an understanding of the mechanism of action for apoptosis induced by TNPs, which can be further used to design safe TNPs for various consumer products and also suggests that extensive research needs to be done on harmful effects of TNPs synthesized from different approaches before commercial application.

Silver nanoparticles engineered by thermal co-reduction approach induces liver damage in Wistar rats: acute and sub-chronic toxicity analysis.

Recently, nanotechnology applications have increased tremendously in consumer products. However, it has been observed that these nanoparticles can cause a potential risk to the environment as well as human health. In the present manuscript, we have analyzed acute and sub-chronic toxicity of engineered silver nanoparticles (AgNPs) by assessing the impact on Wistar rats. AgNPs were synthesized by a novel approach-thermal co-reduction-with spherical shape and a uniform size distribution of 60 nm. The estimated LD50 value was observed to be more than 2000 mg/kg bw in acute toxicity studies. Sub-chronic toxicity indicated impairment of liver and kidney enzymes and various hematological and biochemical parameters. Tissue distribution studies indicated the target organ for accumulation is liver after treatment with AgNP. Particle deposition and congestion was observed in major organs-though, and heart and pancreatic tissues were not affected even by the higher doses. On the basis of the observations of this study, it is concluded that up to 40 mg/kgbw is a safer dose of AgNPs (60 nm, engineered by thermal co-reduction approach) and further research will be required to validate the long-term accumulation in body. In addition, it can also be considered by policymakers for the safer use of AgNPs.

Thermal Co-reduction engineered silver nanoparticles induce oxidative cell damage in human colon cancer cells through inhibition of reduced glutathione and induction of mitochondria-involved apoptosis.

Silver nanoparticles (AgNPs) are being commercialized in a number of consumer products including food and cosmetics where there is a direct exposure of AgNPs to human body. An extensive toxicological evaluation is necessary to understand the mechanism for its safe use, since the toxicity effect varies greatly with the synthesis protocol followed. In this study, we report the detailed toxicological analysis of AgNPs fabricated by thermal co-reduction approach. Our study was analysed in human colon cancer cell line (HCT 116) and the IC50 was calculated as 28.11 µg/ml. It was also observed that AgNP induces oxidative stress on HCT116 by increased levels of lipid peroxidation and reduced levels of glutathione. Mitochondrial membrane depolarization was also analysed and Western blot analysis confirms the increased level of Bcl and Caspase-3 which indicates the mitochondrial -mediated apoptosis. Additionally, flow cytometric analysis suggests cell cycle arrest in G2/M phase. Thus, our study can be a basis for further research to design safe AgNPs in various consumer products. Additionally, similar research can be conducted for different size and shape of AgNP or nano-silver can be engineered using different approaches.

Titanium dioxide nanoparticle-protein interaction explained by docking approach.

Titanium dioxide has been proven for toxicity by in vitro and in vivo approaches, however, further studies are needed in nano-toxicological research using in silico analysis. In this study, Autodock 4.0.5 was used in an attempt to evaluate the interaction of titanium dioxide with proteins. Different cellular proteins were sorted to study the interaction, binding sites, and active sites as a pocket. These pockets have been determined using CastP - an online server. The analysis for the docked structures was performed with regard to the most efficient binding with amino acids. This study is the first of its kind to report on the in silico docking interaction of titanium dioxide nanoparticles without any surface modification. The higher negative binding energy shows strong binding of titanium dioxide with proteins. A strong interaction with different cellular proteins was observed, and more specifically, titanium dioxide nanoparticles showed frequent interaction with proline, lysine, as well as leusine.

Formulation of vitamin D encapsulated cinnamon oil nanoemulsion: Its potential anti-cancerous activity in human alveolar carcinoma cells.

Cinnamon oil is used for medicinal purpose since ancient time because of its antioxidant activity. Oil-in-water nanoemulsion (NE) of cinnamon oil was formulated using cinnamon oil, nonionic surfactant Tween 80 and water by ultrasonication technique. Phase diagram was constructed to investigate the influence of oil, water and surfactant concentration. Vitamin D encapsulated cinnamon oil NE was fabricated by wash out method followed by ultrasonication in similar fashion. The hydrodynamic size of cinnamon oil NE and vitamin D encapsulated cinnamon oil NE was observed as 40.52 and 48.96 nm in complete DMEM F12 media respectively. We focused on the cytotoxic and genotoxic responses of NEs in A549 cells in concentration dependent manner. We observed that both NEs induce DNA damage along with corresponding increase in micronucleus frequency that is evident from the comet and CBMN assay. Both the NEs arrested the cell cycle progression in G0/G1 phase, showed increased expression of Bax, capase-3 and caspase-9 and decrease expression of BcL2 proteins along with significant (p < 0.05) increase in apoptotic cell population and loss of mitochondrial membrane potential. NEs were also evaluated for bactericidal efficacy against E. coli. Thus, both NEs have cytotoxic, genotoxic and antibacterial potential and hence can also be used in food industry with cinnamon oil as carrier for lipophilic nutraceutical like vitamin D.

Fish oil based vitamin D nanoencapsulation by ultrasonication and bioaccessibility analysis in simulated gastro-intestinal tract.

Recently, nanoemulsions have been employed for different applications including food and drug industries for efficient nutrient delivery system. In this study, vitamin D (a lipophilic molecule) was encapsulated in fish oil for higher oral bioavailability. The oil-in-water nanoemulsion was formulated by ultrasonication technique with a droplet size range of 300-450nm and a shelf life of more than 90days. The influence of oil, water and surfactant concentration was investigated by phase diagram. The formulated nanoemulsion had encapsulation efficiency in the range of 95.7-98.2%. Further, nanoemulsion passed through simulated gastro-intestinal tract revealed an increased bioavailability than non-encapsulated vitamin. Thus, the formulation can be used as a drug delivery vehicle for various lipophilic compounds. Till date, no one have fabricated an efficient nano-vehicle for the delivery of vitamin D as well as analyzed the efficient delivery system in simulated GI-tract, this is first of its kind study in this regard. This can be scaled up further after analyzing the safety aspects.

A spectroscopic study on interaction between bovine serum albumin and titanium dioxide nanoparticle synthesized from microwave-assisted hybrid chemical approach.

The use of nanoparticles in food or pharma requires a molecular-level perceptive of how NPs interact with protein corona once exposed to a physiological environment. In this study, the conformational changes of bovine serum albumin (BSA) were investigated in detail when exposed to different concentration of titanium dioxide nanoparticle by various techniques. To analyze the effects of NPs on proteins, the interaction between bovine serum albumin and titanium dioxide nanoparticles at different concentrations were investigated. The interaction, BSA conformations, kinetics, and adsorption were analyzed by dynamic light scattering, Fourier transform infrared spectroscopy and fluorescence quenching. Dynamic light scattering analysis confirms the interaction with major changes in the size of the protein. Fluorescence quenching analysis confirms the side-on or end-on interaction of 1.1 molecules of serum albumin to titanium dioxide nanoparticles. Further, pseudo-second order kinetics was determined with equilibrium contact time of 20min. The spectroscopic analysis suggests that there is a conformational change both at secondary and tertiary structure levels. A distortion in both α-helix and ß-sheets was observed by Fourier transform infrared (FTIR) spectroscopy. Fluorescence quenching analysis confirms the interaction of a molecule of bovine serum albumin to the single TiO2 nanoparticle. Further, pseudo-second order kinetics was determined with equilibrium contact time of 20min. The data of the present study determines the detailed evaluation of BSA adsorption on TiO2 nanoparticle along with mechanism and adsorption kinetics.

Bovine serum albumin interacts with silver nanoparticles with a "side-on" or "end on" conformation.

As the nanoparticles (NPs) enter into the biological interface, they have to encounter immediate and first exposure to many proteins of different concentrations. The physicochemical interaction of NPs and proteins is greatly influenced not only by the number and type of proteins; but also the surface chemistry of NPs. To analyze the effects of NPs on proteins, the interaction between bovine serum albumin (BSA) and silver nanoparticles (AgNPs) at different concentrations were investigated. The interaction, BSA conformations, kinetics and adsorption were analyzed by UV-Visible spectrophotometer, dynamic light scattering (DLS), FT-IR spectroscopy and fluorescence quenching. DLS, FTIR and UV-visible spectrophotometric analysis confirms the interaction with minor alterations in size of the protein. Fluorescence quenching analysis confirms the side-on or end-on interaction of 1.5 molecules of BSA to AgNP. Further, pseudo-second order kinetics was determined with equilibrium contact-time of 30 min. The data of the present study determines the detailed evaluation of BSA adsorption on AgNP along with mechanism, kinetics and isotherm of the adsorption.

Microwave-irradiation-assisted hybrid chemical approach for titanium dioxide nanoparticle synthesis: microbial and cytotoxicological evaluation.

Titanium dioxide nanoparticles (TNPs) are widely used in the pharmaceutical and cosmetics industries. It is used for protection against UV exposure due to its light-scattering properties and high refractive index. Though TNPs are increasingly used, the synthesis of TNPs is tedious and time consuming; therefore, in the present study, microwave-assisted hybrid chemical approach was used for TNP synthesis. In the present study, we demonstrated that TNPs can be synthesized only in 2.5 h; however, the commonly used chemical approach using muffle furnace takes 5 h. The activity of TNP depends on the synthetic protocol; therefore, the present study also determined the effect of microwave-assisted hybrid chemical approach synthetic protocol on microbial and cytotoxicity. The results showed that TNP has the best antibacterial activity in decreasing order from Escherichia coli, Bacillus subtilis, and Staphylococcus aureus. The IC50 values of TNP for HCT116 and A549 were found to be 6.43 and 6.04 ppm, respectively. Cell death was also confirmed from trypan blue exclusion assay and membrane integrity loss was observed. Therefore, the study determines that the microwave-assisted hybrid chemical approach is time-saving; hence, this technique can be upgraded from lab scale to industrial scale via pilot plant scale. Moreover, it is necessary to find the mechanism of action at the molecular level to establish the reason for greater bacterial and cytotoxicological toxicity. Graphical abstract A graphical representation of TNP synthesis.

Thermal co-reduction approach to vary size of silver nanoparticle: its microbial and cellular toxicology.

In recent years, silver nanoparticles (AgNPs) have attracted considerable interest in the field of food, agriculture and pharmaceuticals mainly due to its antibacterial activity. AgNPs have also been reported to possess toxic behavior. The toxicological behavior of nanomaterials largely depends on its size and shape which ultimately depend on synthetic protocol. A systematic and detailed analysis for size variation of AgNP by thermal co-reduction approach and its efficacy toward microbial and cellular toxicological behavior is presented here. With the focus to explore the size-dependent toxicological variation, two different-sized NPs have been synthesized, i.e., 60 nm (Ag60) and 85 nm (Ag85). A detailed microbial toxicological evaluation has been performed by analyzing minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), diameter of inhibition zone (DIZ), growth kinetics (GrK), and death kinetics (DeK). Comparative cytotoxicological behavior was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. It has been concluded by this study that the size of AgNPs can be varied, by varying the concentration of reactants and temperature called as "thermal co-reduction" approach, which is one of the suitable approaches to meet the same. Also, the smaller AgNP has shown more microbial and cellular toxicity.

Biosorption of Cr(VI) by Ceratocystis paradoxa MSR2 using isotherm modelling, kinetic study and optimization of batch parameters using response surface methodology.

This study is focused on the possible use of Ceratocystis paradoxa MSR2 native biomass for Cr(VI) biosorption. The influence of experimental parameters such as initial pH, temperature, biomass dosage, initial Cr(VI) concentration and contact time were optimized using batch systems as well as response surface methodology (RSM). Maximum Cr(VI) removal of 68.72% was achieved, at an optimal condition of biomass dosage 2 g L(-1), initial Cr(VI) concentration of 62.5 mg L(-1) and contact time of 60 min. The closeness of the experimental and the predicted values exhibit the success of RSM. The biosorption mechanism of MSR2 biosorbent was well described by Langmuir isotherm and a pseudo second order kinetic model, with a high regression coefficient. The thermodynamic study also revealed the spontaneity and exothermic nature of the process. The surface characterization using FT-IR analysis revealed the involvement of amine, carbonyl and carboxyl groups in the biosorption process. Additionally, desorption efficiency of 92% was found with 0.1 M HNO3. The Cr(VI) removal efficiency, increased with increase in metal ion concentration, biomass concentration, temperature but with a decrease in pH. The size of the MSR2 biosorbent material was found to be 80 µm using particle size analyzer. Atomic force microscopy (AFM) visualizes the distribution of Cr(VI) on the biosorbent binding sites with alterations in the MSR2 surface structure. The SEM-EDAX analysis was also used to evaluate the binding characteristics of MSR2 strain with Cr(VI) metals. The mechanism of Cr(VI) removal of MSR2 biomass has also been proposed.