Multiparametric Profiling of Engineered Nanomaterials: Unmasking the Surface Coating Effect

Area of Science:

• Nanomaterial science
• Toxicology
• Cellular biology

Background:

• Understanding engineered nanomaterials' (ENMs) cytotoxicity is crucial but challenging.
• Properties driving ENM cytotoxicity remain poorly understood.
• Existing in vitro assays may not capture the full spectrum of cellular responses.

Purpose of the Study:

• To investigate the properties driving ENM cytotoxicity.
• To correlate in vitro cytotoxicity with omics-based cellular responses.
• To elucidate the role of surface chemistry and core composition in ENM-induced effects.

Main Methods:

• Screening of 31 ENMs with diverse core chemistries and surface modifications.
• Utilizing conventional in vitro cytotoxicity assays and omics approaches (proteomics, microarrays).
• Employing multiplex-based cytokine profiling and cell-based validation assays.

Main Results:

• Good concordance observed between primary macrophages and THP-1 cell lines for cytotoxicity and cytokine profiling.
• Low-dose ENM exposure induced nonspecific stress responses (proteomics) and significant gene expression changes (microarrays) dependent on surface modification and core chemistry.
• Cationic ENMs downregulated DNA replication/cell cycle and upregulated inflammatory responses, correlating with cytotoxicity.
• Noncytotoxic PEGylated ENMs induced virus-like transcriptional responses.
• Cytotoxicity did not always correlate with transcriptional effects.

Conclusions:

• Surface chemistry is a primary determinant of cellular responses to ENMs.
• Multiparametric approaches are essential for a comprehensive understanding of ENM-cell interactions.
• Conventional cytotoxicity assays alone are insufficient to predict the full biological impact of ENMs.