Single-cell mass cytometry and multiplexed imaging platforms: Biological insight of advanced nanomaterials, nanoparticles, and nanopollutants

Advances in nanotechnology have introduced a diverse range of nanomaterials with transformative potential for biomedical applications, spanning drug delivery and imaging to immunotherapy and diagnostics. However, their increasing use in clinical and environmental contexts raises pressing questions about their interactions with biological systems, safety, and long-term impact. Single-cell mass cytometry by time-of-flight (CyTOF) and imaging-based mass cytometry approaches have emerged as powerful high-dimensional platforms capable of resolving complex bio–nano interactions at the single-cell level. This review represents the first comprehensive integration of the application of CyTOF and multiplexed imaging platforms in the context of both nanomaterials and environmental nanoparticles, thereby establishing a conceptual framework for their combined biomedical and environmental implications. Importantly, this review does not simply merge two fields but establishes a unified framework to interpret nano–bio interactions. We show that nanomaterials-induced cellular responses are governed by shared single-cell mechanisms across both biomedical and environmental contexts, revealing common principles that cannot be identified through separate analyses. We highlight the integration of CyTOF into nanomaterial research, illustrating how it enables quantitative, multiplexed profiling of nanomaterial uptake, biodistribution, immune modulation, and cellular stress responses across heterogeneous cell populations. Key studies are summarized on gold and silver nanoparticles, graphene, MXenes, transition metal dichalcogenides (TMDs), nanoplastics, and advanced nanocarriers, demonstrating the versatility of CyTOF in both biomedical and environmental nanotoxicology. The ability of this technology to couple cellular phenotyping with nanomaterial tracking provides mechanistic insights into immunological compatibility, therapeutic efficacy, and potential adverse effects. Despite these advances, challenges remain in integrating CyTOF with transcriptomics, proteomics, and imaging mass cytometry to create multi-omics frameworks for precision nanomedicine. Collectively, this review underscores the unique role of CyTOF in bridging nanotechnology and systems biology, offering a path toward safer, more effective, and clinically translatable nanotherapeutics.