Examining the Holy Grail of Nanotechnology: Safe By Design

Engineered nanomaterials (ENM) represent a significant breakthrough in material design and development. The quantum properties that emerge from their scale, precise architecture, and engineering attributes provide considerable opportunity to solve problems in such diverse areas as medicine, electronics, energy, space exploration, water purification, and food storage. Numerous research articles have examined the sensitivity of the relationship of scale, structure, composition, and emergent properties of nanomaterials to their behavior in biological systems and the environment.

This relationship between precise design and behavior has led to the proposal that nanomaterials can be engineered to be Safe By Design (SxD), that is, designed to maximize their benefit in problem solving and product development while posing minimal risk to human health and the environment. While SxD is an extremely attractive concept, it may be useful to examine the assumptions that underlie it, as well as the consequences that might be engendered by it. The proceeding examination is necessarily selective and intended to be thought provoking, not comprehensive.

Firstly, SxD presupposes the existence of crosscutting design principles for ENM in biological systems. It suggests that, in contrast to the concept of a sensitive design-behavior relationship, that there are physical and chemical properties of ENM, or a subset of such properties, that support a given biological behavior in multiple microenvironments. Given the exponential number of combinations of physical and chemical properties possible for an ENM, this assumption seems plausible, albeit challenging to test on a scale that would be definitive.

SxD also suggests that researchers can identify the physical and chemical properties, or the subset of properties, that produce distinct sets of beneficial or adverse effects. Biologically, one might anticipate that the ENM properties designated beneficial or adverse represent two ends of a continuum, with most of the biological behavior occurring between the two poles. (For example, consider a continuum from positive to negative surface charge or from hydrophillicity to hydrophobicity.)

Additionally, SxD assumes that the adverse effect can be engineered out through manipulation of physical and chemical properties while the beneficial properties are maintained. This line of thought suggests that modifications to an ENM that "tweak" a product to decrease risk of an adverse effect can be made without significantly changing the benefit the ENM confers on a product.

If this proves true, it would seem to imply that there are limited unique design solutions but multiple combinations of physical and chemical properties that produce the same effect. The SxD challenge then would be to identify the sets of physical and chemical properties that produce the same outcome in multiple microenvironments, as well as the combination of physical and chemical properties that produces multiple, microenvironment-dependent outcomes.

As a final consideration, increasing attention is being given to life cycle analysis of an ENM, or to potential changes in physical and chemical properties as ENM move through the environment or the human body. Recent research suggests that when an ENM is exposed to a microenvironment, a corona of inorganic environmental substances or biological molecules form around the ENM; that the composition of this corona is a function of the ENM surface properties and the microenvironment; and that the biological response to the ENM is a function of molecules comprising the corona. This hypothesis provides support for SxD in that the number of molecules that could form the corona is more limited than the possible combinations of physical and chemical properties, as well as modifications and derivatives of ENM that could be constructed.

SxD is an intriguing concept with the potential to guide ENM product design and development to maximize benefit and minimize risk to humans and their environment. Broad principles that relate physical and chemical properties to behavior could be determined from careful selection and testing of ENM and microenvironments, however one should consider the cost benefit ratio that would underlie this extensive investigation of design principles in contrast to the perhaps less expensive product-specific analysis of risk and benefit.