Monitoring characteristics and genotoxic effects of engineered nanoparticle-protein corona.

Engineered nanoparticles (ENPs) possess different physical and chemical properties compared to their bulk counterparts. These unique properties have found application in various products in the area of therapeutics, consumer goods, environmental remediation, optical and electronic fields. This has also increased the likelihood of their release into the environment thereby affecting human health and ecosystem. ENPs, when in contact with the biological system have various physical and chemical interactions with cellular macromolecules including proteins. These interactions lead to the formation of protein corona around the ENPs. Consequently, living systems interact with the protein-coated ENP rather than with a bare ENP. This ENP-protein interaction influences uptake, accumulation, distribution and clearance and thereby affecting the cytotoxic and genotoxic responses. Although there are few studies which discussed the fate of ENPs, there is a need for extensive research in the field of ENPs, to understand the interaction of ENPs with biological systems for their safe and productive application.

Cell cycle dependent cellular uptake of zinc oxide nanoparticles in human epidermal cells.

Metal oxide nanoparticles (NPs), including zinc oxide (ZnO) NPs have shown success for use as vehicles for drug delivery and targeting gene delivery in many diseases like cancer. Current anticancer chemotherapeutics fail to effectively differentiate between cancerous and normal cells. There is an urgent need to develop novel drug delivery system that can better target cancer cells while sparing normal cells and tissues. Particularly, ZnO NPs exhibit a high degree of cancer cell selectivity and induce cell death, oxidative stress, interference with the cell cycle progression and genotoxicity in cancerous cells. In this scenario, effective cellular uptake of NP seems to be crucial, which is shown to be affected by cell cycle progression. In the present study, the cytotoxic potential of ZnO NPs and the effect of different cell cycle phases on the uptake of ZnO NPs were examined in A431 cells. It is shown that the ZnO NPs led to cell death and reactive oxygen species generation and were able to induce cell cycle arrest in S and G2/M phase with the higher uptake in G2/M phase compared with other phases.

Navigating the challenges and exploring the perspectives associated with emerging novel biomaterials.

The field of biomaterials is a continuously evolving interdisciplinary field encompassing biological sciences, materials sciences, chemical sciences, and physical sciences with a multitude of applications realized every year. However, different biomaterials developed for different applications have unique challenges in the form of biological barriers, and addressing these challenges simultaneously is also a challenge. Nevertheless, immense progress has been made through the development of novel materials with minimal adverse effects such as DNA nanostructures, specific synthesis strategies based on supramolecular chemistry, and modulating the shortcomings of existing biomaterials through effective functionalization techniques. This review discusses all these aspects of biomaterials, including the challenges at each level of their development and application, proposed countermeasures for these challenges, and some future directions that may have potential benefits.

Dopamine-Functionalized, Red Carbon Quantum Dots for In Vivo Bioimaging, Cancer Therapeutics, and Neuronal Differentiation.

One of the crucial requirements of quantum dots for biological applications is their surface modification for very specific and enhanced biological recognition and uptake. Toward this end, we present the green synthesis of bright, red-emitting carbon quantum dots derived from mango leaf extract (mQDs). These mQDs are conjugated electrostatically with dopamine to form mQDs-dopamine (mQDs:DOPA) bioconjugates. Bright-red fluorescence of mQDs was used for bioimaging and uptake in cancerous and noncancerous cell lines, tissues, and in vivo models like zebrafish. mQDs exhibited the highest uptake in brain tissue compared to the heart, kidney, and liver. mQD:DOPA conjugates killed breast cancer cells and increased uptake in epithelial RPE-1 cells and zebrafish. Additionally, mQDs:DOPA promoted neuronal differentiation of SH-SY5Y cells to differentiated neurons. Both mQDs and mQDs:DOPA exhibited the potential for higher collective cell migrations, implicating their future potential as next-generation tools for advanced biological and biomedical applications.

New insight into long-term effects of phthalates microplastics in developing zebrafish: Evidence from genomic alteration and organ development.

The plasticizer leaches from the microplastics are one of the significant concerns related to plastic pollution. These plasticizers are known to be endocrine disrupters; however, little is known about their long-term effect on the development of aquatic vertebrates. Hence, the present study has been conducted to provide a holistic understanding of the effect of the three most common plasticizers, dibutyl phthalate (DBP), diethyl phthalate (DEP), and di-ethylhexyl phthalate (DEHP) leaching out from the microplastics in zebrafish development. Zebrafish larvae were exposed to different phthalates at different concentrations. The phthalates have shown significantly higher mortality and morphological changes in the larva upon exposure compared to the control. A significant change in the genes related to cardiovascular development (krit1, fbn2b), dorsoventral axis development (chrd, smad5), tail formation (pkd2, wnt3a, wnt8a), and floorplate development (foxa2) were also observed under the effects of the phthalates in comparison to control.

Tissue-Derived Primary Cell Type Dictates the Endocytic Uptake Route of Carbon Quantum Dots and In Vivo Uptake.

Carbon quantum dots (CQDs) require systemic biological delivery to advance their applications in drug delivery, biosensing, and bioimaging. We describe the endocytic pathways of green-emitting fluorescent carbon quantum dots (GCQDs) with sizes varying from 3 to 5 nm in mouse tissue-derived primary cells, tissues, and zebrafish embryos. The GCQDs demonstrated cellular internalization into mouse kidney and liver primary cells via a clathrin-mediated pathway. Using imaging, we were able to identify and reinforce the animal's body features in terms of different tissues exhibiting differential affinity for these CQDs, which will be extremely beneficial in the development of next-generation bioimaging and therapeutic scaffolds based on carbon-based quantum dots.

Spatiotemporal dynamics of DNA nanocage uptake in zebrafish embryos for targeted tissue bioimaging applications.

Three-dimensional DNA nanocages have attracted significant attention for various biomedical applications including targeted bioimaging in vivo. Despite the numerous advantages, the use and in vivo exploration of DNA nanocages are limited as the cellular targeting and intracellular fate of these DNA nanocages within various model systems have not been explored well. Herein, using a zebrafish model system, we provide a detailed understanding of time-, tissue- and geometry-dependent DNA nanocage uptake in developing embryos and larvae. Of all the geometries tested, tetrahedrons showed significant internalization in 72 hours post-fertilized larvae upon exposure, without disturbing the expression of genes involved in embryo development. Our study provides a detailed understanding of the time and tissue-specific uptake of DNA nanocages in the zebrafish embryos and larvae. These findings will provide valuable insights into the internalization and biocompatible potential of DNA nanocages and will help to predict their candidature for biomedical applications.

A critical review on the role of abiotic factors on the transformation, environmental identity and toxicity of engineered nanomaterials in aquatic environment.

Engineered nanomaterials (ENMs) are at the forefront of many technological breakthroughs in science and engineering. The extensive use of ENMs in several consumer products has resulted in their release to the aquatic environment. ENMs entering the aquatic ecosystem undergo a dynamic transformation as they interact with organic and inorganic constituents present in aquatic environment, specifically abiotic factors such as NOM and clay minerals, and attain an environmental identity. Thus, a greater understanding of ENM-abiotic factors interactions is required for an improved risk assessment and sustainable management of ENMs contamination in the aquatic environment. This review integrates fundamental aspects of ENMs transformation in aquatic environment as impacted by abiotic factors, and delineates the recent advances in bioavailability and ecotoxicity of ENMs in relation to risk assessment for ENMs-contaminated aquatic ecosystem. It specifically discusses the mechanism of transformation of different ENMs (metals, metal oxides and carbon based nanomaterials) following their interaction with the two most common abiotic factors NOM and clay minerals present within the aquatic ecosystem. The review critically discusses the impact of these mechanisms on the altered ecotoxicity of ENMs including the impact of such transformation at the genomic level. Finally, it identifies the gaps in our current understanding of the role of abiotic factors on the transformation of ENMs and paves the way for the future research areas.

Combination of humic acid and clay reduce the ecotoxic effect of TiO2 NPs: A combined physico-chemical and genetic study using zebrafish embryo.

The series of breakthroughs that have occurred within the realm of nanotechnology have been the source of several new products and technological interventions. One of the most salient examples in this regard is the widespread employment of titanium dioxide (TiO2) nanoparticles across a range of consumer goods. Given that waste is generated at every stage of the consumer-product cycle (from production to disposal), many items with TiO2 nanoparticles are likely to end up being discarded into water bodies. In order to understand the interaction of TiO2 NPs with aquatic ecosystem, the ecological fate and toxicity of TiO2 NPs was studied by exposing zebrafish embryos to a combination of abiotic factors (humic acid and clay) to assess its effect on the development of zebrafish embryos. The physiological changes were correlated with genetic marker analysis to holistically understand the effect on embryos development. Derjaguin-Landau-Verwey-Overbeek (DLVO) theory was used to analyze the interaction energy between TiO2 NPs and natural organic matter (NOM) for understanding the aggregation behavior of engineered nanoparticles (ENPs) in media. The study revealed that combination of HA and clay stabilized TiO2 NPs, compared to bare TiO2 and HA or clay alone. TiO2 NPs and TiO2 NPs + Clay significantly altered the expression of genes involved in development of dorsoventral axis and neural network of zebrafish embryos. However, the presence of HA and HA + clay showed protective effect on zebrafish embryo development. The complete system analysis demonstrated the possible ameliorating effects of abiotic factors on the ecotoxicity of ENPs.

Nanotherapeutics for the Treatment of Cancer and Arthritis.

BACKGROUND: Nanotechnology is gaining significant attention worldwide for the treatment of complex diseases such as AIDS (acquired immune deficiency syndrome), cancer and rheumatoid arthritis. Nanomedicine is the application of nanotechnology used for diagnosis and treatment for the disease that includes the preservation and improvement of human health by covering an area such as drug delivery using nanocarriers, nanotheranostics and nanovaccinology. The present article provides an insight into several aspects of nanomedicine such as usages of multiple types of nanocarriers, their status, advantages and disadvantages with reference to cancer and rheumatoid arthritis. METHODS: An extensive search was performed on the bibliographic database for research article on nanotechnology and nanomedicine along with looking deeply into the aspects of these diseases, and how all of them are co-related. We further combined all the necessary information from various published articles and briefed to provide the current status. RESULTS: Nanomedicine confers a unique technology against complex diseases which includes early diagnosis, prevention, and personalized therapy. The most common nanocarriers used globally are liposomes, polymeric nanoparticles, dendrimers, metallic nanoparticles, magnetic nanoparticles, solid lipid nanoparticles, polymeric micelles and nanotubes among others. CONCLUSION: Nanocarriers are used to deliver drugs and biomolecules like proteins, antibody fragments, DNA fragments, and RNA fragments as the base of cancer biomarkers.

Montmorillonite clay and humic acid modulate the behavior of copper oxide nanoparticles in aqueous environment and induces developmental defects in zebrafish embryo.

Copper oxide nanoparticles (CuO NPs) is one of the most commonly used metal oxide nanoparticles for commercial and industrial products. An increase in the manufacturing and use of the CuO NPs based products has increased the likelihood of their release into the aquatic environment. This has attracted major attention among researchers to explore their impact in human as well as environmental systems. CuO NPs, once released into the environment interact with the biotic and abiotic constituents of the ecosystem. Hence the objective of the study was to provide a holistic understanding of the effect of abiotic factors on the stability and aggregation of CuO NPs and its correlation with their effect on the development of zebrafish embryo. It has been observed that the bioavailability of CuO NPs decrease in presence of humic acid (HA) and heteroagglomeration of CuO NPs occurs with clay minerals. CuO NPs, CuO NPs + HA and CuO NPs + Clay significantly altered the expression of genes involved in development of dorsoventral axis and neural network of zebrafish embryos. However, the presence of HA with clay showed protective effect on zebrafish embryo development. These findings provide new insights into the interaction of NPs with abiotic factors and combined effects of such complexes on developing zebrafish embryos genetic markers.

Impact of humic acid on the fate and toxicity of titanium dioxide nanoparticles in Tetrahymena pyriformis and zebrafish embryos.

The extensive usage of titanium dioxide (TiO2) nanoparticles in daily usage products have increased their release into the environment. The present study has attempted to investigate the behaviour of titanium dioxide (TiO2) nanoparticles in different experimental buffers in the presence of humic acid. Also, the effect of TiO2 nanoparticles was assessed in different aquatic organisms with and without the presence of humic acid. The results demonstrate that humic acid increases the dispersion of TiO2 nanoparticles via its adsorption on the surface of the nanoparticles, mainly due to electrostatic interactions. The maximum aggregation was observed in the zebrafish growth medium (E3 medium) even in the presence of humic acid. The intensity of TiO2 nanoparticle sedimentation was observed in the order: E3 media > Dryl's buffer > MilliQ water. Interestingly, the ecotoxicity results for Tetrahymena pyriformis and Danio rerio showed that the presence of humic acid reduces the toxicity of TiO2 nanoparticles.

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.

Cellular internalization and antioxidant activity of cerium oxide nanoparticles in human monocytic leukemia cells.

Overproduction of free radicals contributes to oxidative stress and inflammation leading to various disease conditions. Cerium oxide nanoparticles (nanoceria) have been shown to scavenge free radicals and have the potential for being used as a therapeutic agent in disease conditions. Therefore, in the present study, human monocytic leukemia cells (THP-1) were used as a model to evaluate the uptake and free radical scavenging activity of nanoceria. Our data showed a significant (P<0.05) increase in the internalization of nanoceria in a concentration-dependent (10-100 µg/mL) manner in THP-1 cells. Although no cytotoxicity was observed at these concentrations, nanoceria significantly (P<0.05) reduced the amount of reactive oxygen species. This was evident by a significant (P<0.05) decrease in the 2,7-dichlorofluorescein diacetate fluorescence observed in flow cytometry and fluorescence microscopy. The present study shows that nanoceria have therapeutic potential in diseases such as cancer.

Curcumin Ag nanoconjugates for improved therapeutic effects in cancer.

Curcumin has a broad spectrum of pharmacological activities, one of them is anticancer activity that is mediated through multiple mechanisms. The major disadvantage associated with the use of curcumin is its low bioavailability due to its poor aqueous solubility. Nanoformulations of curcumin provide an effective solution for this problem. In this study, we have synthesized curcumin Ag nanoconjugates and evaluated their anticancer potential.

Synthesis of biocompatible iron oxide nanoparticles as a drug delivery vehicle.

Over the last decade, there has been growing interest in developing novel nanoparticles (NPs) for biomedical applications. A safe-by-design approach was used in this study to synthesize biocompatible iron oxide NPs. The size of the particles obtained was ~100 nm. Although these NPs were significantly (P<0.05) internalized in MCF-7 (human breast adenocarcinoma cell line) cells, no adverse effect was observed in the cells as assessed by cytotoxicity assays (neutral red uptake and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) and cell cycle analysis. Our data demonstrate the potential of iron oxide NPs as a biocompatible carrier for targeted drug delivery.

TiO2 nanoparticles induce DNA double strand breaks and cell cycle arrest in human alveolar cells.

TiO2 nanoparticles (NPs) have the second highest global annual production (∼3000 tons) among the metal-containing NPs. These NPs are used as photocatalysts for bacterial disinfection, and in various other consumer products including sunscreen, food packaging, therapeutics, biosensors, surface cleaning agents, and others. Humans are exposed to these NPs during synthesis (laboratory), manufacture (industry), and use (consumer products, devices, medicines, etc.), as well as through environmental exposures (disposal). Hence, there is great concern regarding the health effects caused by exposure to NPs and, in particular, to TiO2 NPs. In the present study, the genotoxic potential of TiO2 NPs in A549 cells was examined, focusing on their potential to induce ROS, different types of DNA damage, and cell cycle arrest. We show that TiO2 NPs can induce DNA damage and a corresponding increase in micronucleus frequency, as evident from the comet and cytokinesis-block micronucleus assays. We demonstrate that DNA damage may be attributed to increased oxidative stress and ROS generation. Furthermore, genomic and proteomic analyses showed increased expression of ATM, P53, and CdC-2 and decreased expression of ATR, H2AX, and Cyclin B1 in A549 cells, suggesting induction of DNA double strand breaks. The occurrence of double strand breaks was correlated with cell cycle arrest in G2/M phase. Overall, the results indicate the potential for genotoxicity following exposure to these TiO2 NPs, suggesting that use should be carefully monitored.