10.1021/acs.nanolett.5b04487.s001 Lu Liu Lu Liu Meiqing Sun Meiqing Sun Haijun Zhang Haijun Zhang Qilin Yu Qilin Yu Mingchun Li Mingchun Li Yu Qi Yu Qi Chengdong Zhang Chengdong Zhang Guandao Gao Guandao Gao Yingjin Yuan Yingjin Yuan Huanhuan Zhai Huanhuan Zhai Wei Chen Wei Chen Pedro J. J. Alvarez Pedro J. J. Alvarez Facet Energy and Reactivity versus Cytotoxicity: The Surprising Behavior of CdS Nanorods American Chemical Society 2016 faceted nanorod nanoparticle reactivity CdS NanorodsResponsible development unicellular microorganisms endoplasmatic reticulum stress Saccharomyces cerevisiae Surprising Behavior nanomaterial surface energy cell viability Facet Energy cytotoxicity increases 2016-01-13 00:00:00 Journal contribution https://acs.figshare.com/articles/journal_contribution/Facet_Energy_and_Reactivity_versus_Cytotoxicity_The_Surprising_Behavior_of_CdS_Nanorods/2089630 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 <i>Saccharomyces cerevisiae</i> 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 Cd<sup>2+</sup> 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.