Nanoparticles may influence mast cells gene expression profiles without affecting their degranulation function

Abstract

An in vitro method for monitoring nanoparticle effects on IgE-dependent mast cell degranulation was developed and validated. The assayed nanoparticles included four clinical-grade nanomedicines (Abraxane, Doxil, AmBisome, and Feraheme) and three commercial research-grade nanomaterials (generation 5 PAMAM dendrimers with carboxy-, hydroxy-, or amine- surface functionalities). Most of the tested materials did not alter IgE-dependent mast cell degranulation, suggesting that nanoparticles and nanomedicines are unlikely to worsen pre-existing allergies to other antigens. Two clinical-grade formulations containing cytotoxic oncology drugs—Abraxane and Doxil—decreased degranulation. Abraxane but not Doxil decreased FcεR expression on the cell surface. Single-cell sequencing revealed the most differentially expressed genes (DEG) in Abraxane and Doxil-treated cultures. Interestingly, Feraheme and amine-terminated dendrimers induced DEG without affecting degranulation. These data demonstrate that some nanomaterials have more effects on immune cells than can be detected by a functional immunoassay.