Life-Cycle Assessment and Toxicity Profiling of Green Nanomaterials: Bridging Sustainability and Biomedical Safety

Abstract

The production of green nanomaterials may utilize renewables as feedstocks, biological reducing agents, aqueous processing, or minimize the use of hazardous reagents, which makes them potentially useful for drug delivery, imaging, diagnostics, tissue engineering, antimicrobial systems, and regenerative medicine. But green synthesis does not necessarily ensure life-cycle sustainability or biomedical safety. This review combines the concepts of life-cycle assessment (LCA), physicochemical characterization, exposure analysis, and toxicity profiling in order to facilitate safe-and-sustainable-by-design development. LCA establishes the functional unit, system boundary, lists material and energy flows, and quantifies burdens related to the acquisition, synthesis, purification, formulation, use, release, recycling, and disposal of feedstock. Toxicity profiling includes the study of size, morphology, composition, crystallinity, surface chemistry, aggregation, dissolution, protein-corona formation, delivered dose, cellular uptake, biodistribution, persistence, and clearance. These endpoints are related to cytotoxicity, oxidative stress, genotoxicity, inflammation, hemocompatibility, immunotoxicity, organ toxicity, reproductive effects and ecotoxicity. Integration is important since reducing energy and/or solvent consumption can affect purity, stability, dose, effectiveness, or toxicity; and safer surface modifications can add to processing requirements.
The use of multi-criteria decision analysis to identify trade-offs, combined with a framework that compares functionally equivalent alternatives, quantifies uncertainty and applies mechanistically relevant models, should be used. The challenges are the incompleteness of the inventory, the lack of consistency in how the dose is measured, biological batch variability, assay interference, lack of long-term studies and inadequate end-of-life transformation data. Quality-by-design manufacturing, harmonized reporting, reference materials, high throughput and new approach methodologies, toxicokinetic modeling, and regulatory alignment are some of the items needed for future translation. When connected to toxicity evidence, LCA can avoid burden shifting and facilitate the development of green nanomaterials to make them good for both the environment and society, and effective for clinical applications.