Nanomaterials are individual blocks of a material of sizes in the range of 1–100 nm and constitute the base to a revolution in all fields under the name nanotechnology. It has attracted great attention to many applications due to their extraordinary physical and chemical, mechanical, magnetic, optical, electrical and piezoelectric properties compared to bulk materials, which offer great promise in the development of nanotechnology to revolutionize the world through promising applications, including industry, agriculture, business, medicine, public health, household appliances, and environment. In particular, nanomaterial have been used in drug delivery, disease detection, and disease treatment applications such as medical imaging, medicine and dentistry, treatments medical device, implantable sensors, drug delivery and dermatology. Moreover, nanomaterials have been integrated for electromechanical and flexible devices, tissue engineering, devices for monitoring cellular signals and Hybrid nano-bio-mechanical system.
The world economy has been significantly affected due to activities related to nanotechnology.( Fig. 1) shows enormous revenue of ∼ $2500 billion that is expected to prevail by 2015 in relation to nanotechnology enabled products. Nanotechnology is growing by leaps and bounds; there are a lot of materials, tools, devices, as well as inventories of nanotechnology based consumer product as described in details in . However, Nanotechnology already is part of our life. Therefore several questions have started to arise e.g., is this technology benign? How about their interactions with cells or human organisms? How would be the regulations on a scale?
Considering the above questions and summarizing the possible hazards of nanoparticles (NPs) there will be a future need for analyzing the presence and properties of NPs in samples from humans, animals, the environment and commercial products. Such routine analyses needs to be user-friendly, robust and standardized to allow for a cost-effective flow of various NP-containing samples. The development of routine analytical techniques for the detection and characterization of NPs do however face two major problems. The first is the isolation of the NPs. Collection, filtering and extraction of the NPs has shown to be associated with aggregation thus giving false data in the subsequent characterization steps. NPs special chemical and physical properties have previously not been a factor accounted for when developing the techniques for filtering and chromatography used as standards today. The stability index of the nanoparticle in this aspect is another important issue needs to be addressed . The need for isolating both metallic and organic NPs from the same samples means facing another challenge previously unmet. Thus, the development of techniques for isolation of NPs from a wide range of samples without the undesirable aggregation is a first necessary step for analyzing the presence of NPs in our surroundings. The second problem lies in combining the desired analysis techniques needed for characterizing unknown NPs to a simple standard protocol. Characterization of the elemental composition, size, shape and quantity of the NPs are all needed to evaluate their potential hazardous implications. These properties can all be characterized today using different methods such as TEM, ICP-MS, XPS and DLS. These methods are often costly, time-consuming and each requires their degree of expertise. Sometimes prior knowledge of the content of the sample is needed as well. The choice of technique also varies depending on whether metallic or organic NPs are being analyzed. Additionally, some protocols used today rely on a fair degree of purity of the sample. Finding simple robust techniques for analyzing multiple factors in mixed samples without relying on the technical expertise of the user is thus of utmost importance. New scopes on the implications of NPs are continuously published and we steadily begin to acquire some fundamental knowledge on their impact on humans, animals and the environment. The research on routine analyses for detection and characterization of NPs are however virtually nonexistent and given the challenges described this is a trend that needs to change now.
Among the nanomaterial series, metal oxide nano is one of the promising materials have been applied in many applications such as chemical sensors and biosensors, cancer immunotherapy, water treatment, pollution trace detection and environmental improvement, sensors for environmentally hazardous gases. Furthermore, metal oxides based piezoelectric humidity sensors and piezoelectric nanogenerators based devices for converting mechanical energy (such as body movement, muscle stretching, blood pressure, flow of body fluids, blood flow, contraction of blood vessels, dynamic fluid in nature) into electrical energy are also possible applications for self-powering nanodevices and nanosystems for implantation of nanodevices . However, since almost everything can be toxic at an enough dose and nanomaterials behave with different properties at different size and shape for different compound classes, including metals, metal oxides, carbon, and semiconductor nanomaterials. Therefore, the potential negative impacts of nanomaterials on human health and the environment of nanotechnology have become an increasingly active area of research.
Carbon based nanostructured materials also have been attracted considerable attention in recent years due to their fascinating mechanical, electrical, thermal and optical properties. They have been widely used in biological and medical technologies and for a variety of biomedical areas ranging from biosensing, drug delivery, cancer treatment, tissue engineering where the requirement of safety and toxicity is priority. Due to their biocompatible property, they have been commonly used for these applications. However, safety and toxicity issues have not been solved yet and stayed as a question mark . Here, we highlighted safety and toxicity issues of carbon based materials, mainly focusing on graphene and carbon nanotubes.
The diagnostic and therapeutic applications based on carbon nanotubes (CNTs) have been seen as intriguing issues and have recently started to be investigated in environmental, health and safety perspectives . The preliminary results of some studies showed that CNTs are biologically compatible to certain cells and organs however some further studies indicated that CNTs are extremely hazardous that can cause both acute and chronic adverse effects to most of the living system. Though the cellular uptake of CNTs, mechanisms of cytotoxic and how it’s modulated by physicochemical parameters (diameter, length, surface functionalization etc.) are still unclear and needed to be investigated more precisely. It is apparent that, biological effects of CNTs should be considered as sample and case specific. Therefore, the nanotoxicity and safety require continuing and extensive investigations before clinical and biomedical applications.
Although biological-related applications, especially in vivo applications have been taken to ensure for CNTs, a very few studies are available for graphene. Analogously, the toxicity of graphene also depends on some physicochemical parameters. Recently, Zhang et al. compared that, cytotoxicity of graphene to that of CNTs in neuronal PC12 cells. The results showed that toxicity of graphene is size and shape dependent, with having a lower toxicity than CNTs. However in lower concentrations, graphene showed inverse effect between toxicity and concentrations. The other recent study showed that, surface modified graphene nanosheets can be used for photothermal cancer treatment without any adverse effect in toxicity perspective. Although many successful and promising applications have been reached, more detailed and longer-term studies are required before serious in vivo biomedical applications of graphene. As a result, there are many challenges ahead that must be addressed before CNTs and graphene can be successfully integrated into biomedical devices and technology. The main advances required, in our opinions, include the following:
Protocols and fur their experiments should be conducted to determine the exact nature of the nanotoxicity of CNT-based and graphene-based materials.
- Innovative ideas and further experiments are needed to further develop the use of graphene in advanced biomedical applications.
- Innovative solutions are required to reduce fabrication and running costs of CNT and graphene biomedical devices to make them economically viable.
- The long-term goals associated with incorporating CNTs and graphene into biomedical technology suggest that further research is required before these carbon nanostructured devices reach sufficient performance standards.
Recently, study on the assessment of the potential health and environmental risk of metal-based nanomaterials has become important to their increasing production and use. Bianary quantum dot that contains cadmium/selenide has been reported to be toxic to the cell. Thick coatings that increase the diameter of probe are required. Numbers of cell assays studied have been reported in concern to the interaction between nanoparticle and living substances. However, no validated standard or protocol has yet been established. There are also numbers of scientific report concerning the toxicity some metal nanoparticles yet the conclusions seem to be non-consistent. This might due to no standard protocol for assessment of nanomaterials.
It has been reported that, the thermodynamically stable forms of most of the metals are their oxides. More importantly, metal oxides such as SiO2, TiO2, ZnO, have been considered to be ‘GRAS’ (generally recognized as safe) substance by United states food and drug administration (FDA) for decades. Metal oxide are photoactive, the photoactivity of these materials are enhanced when their size is confined at submicron scale. With nanotechnology progress, nanocrystalline metal oxides are being used within a great variety of applications due to their novel optical, magnetic, and electronic properties. With widespread use of these manufactured nanoparticles, concerns about their potential impact on the environment and human health have been raised.
Toxicity of manufactured nanoparticles may be attributed to several different modes of action: chemical toxicity based on chemical composition (e.g., release of toxic ions); surface catalyzed reactions (e.g., formation of reactive oxygen species (ROS)); or stress of stimuli caused by the surface, size, and shape of the particles. Photogeneration of ROS by metal oxides generally involves four processes: (i) generation of electrons and holes by photoexcitation; (ii) migration of the photogenerated charge carriers to the surface; (iii) subsequent reduction/oxidization of the adsorbed reactants directly by electrons/holes for reactive oxygen species (ROS) forming; and (iv) recombination of the photogenerated electron-hole pairs. Phtoenerated ROS by nanocrystalline metal oxides interacting with environmental agents represents another important mode of toxicity. High concentration of ROS photogenerated by nanocrystalline metal oxides causes oxidative stress and can eventually elicit toxicity in biological systems . Wealth of studies have demonstrated phototoxicity of metal oxide nanoparticles in a broad range of biological systems, from bacteria to mammalian cell lines . The shape, size, and morphology of a compound can also play a significant role in its phototoxicity of nanocrystalline metal oxide.
Finally, major breakthroughs in nanotechnology give it an escape velocity from laboratory to “absolute world”. As we want to keep continuing our world green the upcoming concept are coming to use nanomaterials to enhance the environmental sustainability and considering as the green nanotechnology. The very first step of which is to make nanoscale products using nanotechnology in support of sustainability in terms of human health and environment. Now it’s well known that the biocompatibility, bioretention, and biodistribution of nanomaterials do not agree with the rapid pace of manufacturing numerous forms of engineered nanostructures. The present efforts even limited and focused predominantly on exploring novel structures at the nanoscale rather than the novel approaches to make it “greener”, where immediate steps are the demand of the time.
The other concern is, several studies are going in vitro and in vivo with cancer cells but unfortunately, the reports are very limited for nanoparticle interactions with blood cells in circulations. There are some important aspects of such interactions are coming out e.g., interactions of red blood cell (RBC) membranes with different nanoparticle sizes and surface properties for hemocompatibility and the direct interaction of hemoglobin with the nanomaterials. Again it should be noted although RBCs are the majority populated cells in blood, the interactions of nanoparticles with other blood cells and their constituents should be investigated to estimate the safety use of the nanomaterials for biomedical applications.