Facet Energy and Reactivity versus Cytotoxicity: The Surprising Behavior of CdS Nanorods

Responsible development of nanotechnology calls for improved understanding of how nanomaterial surface energy and reactivity affect potential toxicity. Here, we challenge the paradigm that cytotoxicity increases with nanoparticle reactivity. Higher-surface-energy {001}-faceted CdS nanorods (CdS-H) were less toxic to Saccharomyces cerevisiae than lower-energy ({101}-faceted) nanorods (CdS-L) of similar morphology, aggregate size, and charge. CdS-H adsorbed to the yeast’s cell wall to a greater extent than CdS-L, which decreased endocytosis and cytotoxicity. Higher uptake of CdS-L decreased cell viability and increased endoplasmatic reticulum stress despite lower release of toxic Cd²⁺ ions. Higher toxicity of CdS-L was confirmed with five different unicellular microorganisms. Overall, higher-energy nanocrystals may exhibit greater propensity to adsorb to or react with biological protective barriers and/or background constituents, which passivates their reactivity and reduces their bioavailability and cytotoxicity.