Chemical basis of interactions between engineered nanoparticles and biological systems.

As defined by the European Commission, nanomaterial is a natural, incidental or manufactured material containing particles in an unbound state or as an aggregate or agglomerate in which ≥ 50% of the particles in the number size distribution have one or more external dimensions in the size range 1 to 100 nm. In specific cases and where warranted by concerns for the environment, health, safety or competition, the number size distribution threshold of 50% may be replaced with a threshold between 1 and 50%. 1 Engineered nanomaterials (ENMs) refer to man-made nanomaterials. Materials in the nanometer range often possess unique physical, optical, electronic, and biological properties compared with larger particles, such as the strength of graphene,2 the electronic properties of carbon nanotubes (CNTs),3 the antibacterial activity of silver nanoparticles4 and the optical properties of quantum dots (QDs). 5 The unique and advanced properties of ENMs have led to a rapid increase in their application. These applications include aerospace and airplanes, energy, architecture, chemicals and coatings, catalysts, environmental protection, computer memory, biomedicine and consumer products. Driven by these demands, the worldwide ENM production volume in 2016 is conservatively estimated in a market report by Future Markets to be 44,267 tons or ≥ $5 billion.6 As the production and applications of ENMs rapidly expand, their environmental impacts and effects on human health are becoming increasingly significant.7 Due to their small sizes, ENMs are easily made airborne.8 However, no accurate method to quantitatively measure their concentration in air currently exists. A recently reported incident of severe pulmonary fibrosis caused by inhaled polymer nanoparticles in seven female workers obtained much attention.9 In addition to the release of ENM waste from industrial sites, a major release of ENMs to environmental water occurs due to home and personal use of appliances, cosmetics and personal products, such as shampoo and sunscreen.10 Airborne and aqueous ENMs pose immediate danger to the human respiratory and gastrointestinal systems. ENMs may enter other human organs after they are absorbed into the bloodstream through the gastrointestinal or respiratory systems.11,12 Furthermore, ENMs in cosmetics and personal care products, such as lotion, sunscreen and shampoo may enter human circulation through skin penetration.13 ENMs are very persistent in the environment and are slowly degraded. The dissolved metal ions from ENMs can also revert back to nanoparticles under natural conditions.14 ENMs are stored in plants, microbes and animal organs and can be transferred and accumulated through the food chain.15,16 In addition to the accidental entry of ENMs into human and biological systems, ENMs are also purposefully injected into or enter humans for medicinal and diagnostic purposes.17 Therefore, interactions of ENMs with biological systems are inevitable. In addition to engineered nanomaterials, there are also naturally existing nanomaterials such as proteins and DNA molecules, which are key components of biological systems. These materials, combined with lipids and organic and inorganic small molecules, form the basic units of living systems –cells.18 To elucidate how nanomaterials affect organs and physiological functions, a thorough understanding of how nanomaterials perturb cells and biological molecules is required (Figure 1). Rapidly accumulating evidence indicates that ENMs interact with the basic components of biological systems, such as proteins, DNA molecules and cells.19-21 The driving forces for such interactions are quite complex and include the size, shape and surface properties (e.g., hydrophobicity, hydrogen-bonding capability, pi-bonds and stereochemical interactions) of ENMs.22-25 Figure 1 Interactions of nanoparticles with biological systems at different levels. Nanoparticles enter the human body through various pathways, reaching different organs and contacting tissues and cells. All of these interactions are based on nanoparticle-biomacromolecule . Evidence also indicates that chemical modifications on a nanoparticle’s surface alter its interactions with biological systems.26-28 These observations not only support the hypothesis that basic nano-bio interactions are mainly physicochemical in nature but also provide a powerful approach to controlling the nature and strength of a nanoparticle’s interactions with biological systems. Practically, a thorough understanding of the fundamental chemical interactions between nanoparticles and biological systems has two direct impacts. First, this knowledge will encourage and assist experimental approaches to chemically modify nanoparticle surfaces for various industrial or medicinal applications. Second, a range of chemical information can be combined with computational methods to investigate nano-biological properties and predict desired nanoparticle properties to direct experiments.29-31 The literature regarding nanoparticle-biological system interactions has increased exponentially in the past decade (Figure 2). However, a mechanistic understanding of the chemical basis for such complex interactions is still lacking. This review intends to explore such an understanding in the context of recent publications. Figure 2 An analysis of literature statistics indicates growing concern for the topics that are the focus of this review. The number of publications and citations were obtained using the keywords “nanoparticles” and “biological systems” . A breakthrough technology cannot prosper without wide acceptance from the public and society; that is, it must pose minimal harm to human health and the environment. Nanotechnology is now facing such a critical challenge. We must elucidate the effects of ENMs on biological systems (such as biological molecules, human cells, organs and physiological systems). Accumulating experimental evidence suggests that nanoparticles interact with biological systems at nearly every level, often causing unwanted physiological consequences. Elucidating these interactions is the goal of this review. This endeavor will help regulate the proper application of ENMs in various products and their release into the environment. A more significant mission of this review is to direct the development of “safe-by-design” ENMs, as their demands for and applications continue to increase.