Advancing food nanotoxicology with microphysiological systems: Rebalancing the risk/benefit ratio toward safer nano-enabled food innovations

Background

Incorporating nanomaterials into food products provides key benefits, including extended shelf life, improved safety, and enhanced quality and texture. These innovations could help tackle major challenges in modern food systems, such as reducing waste and enhancing food quality and safety. However, potential toxicity remains a concern, compounded by the lack of physiologically relevant models for assessing ingested nanomaterials. Traditional in vitro and in vivo approaches often fail to mimic gastrointestinal complexity, resulting in inconsistent and non-predictive nanotoxicity data that hinder accurate risk assessment of nano-enabled foods.

Scope and approach

To address this gap, this review evaluates the potential of microphysiological systems (MPS), particularly gut-targeted MPS, for modeling gastrointestinal nanoparticle exposure. It examines how MPS technologies replicate key physiological processes relevant to food-specific risk assessment, including intestinal barrier function, microbiota–immune interactions, and gut–organ communication. A comparative analysis of technological advances and their applications in nanotoxicology explores how MPS can be better adapted for nanofood safety evaluation.

Key findings

MPS technology offers a powerful tool for modeling the gastrointestinal tract by replicating key physiological features such as barrier function, microbiome-immune interactions, and gut–organ axes. However, its application in food nanotoxicology remains limited, and its full potential, particularly for microbiome–immune integration, has yet to be realized. Key challenges include sustaining long-term co-cultures, simulating digestion, and modeling nanoparticle biotransformation. Additionally, standardization, reproducibility, and regulatory alignment hinder broader adoption. This review outlines strategies to address these barriers, including AI integration and multidisciplinary frameworks to support MPS validation and regulatory uptake in nanofood safety.