Quantum dots (QDs) are a type of nanoparticle with excellent optical properties, suitable for many optical-based biomedical applications. However, the potential of quantum dots to be used in clinical settings is limited by their toxicity. As such, much effort has been invested to examine the mechanism of QDs’ toxicity. Yet, the current literature mainly focuses on ROS- and apoptosis-mediated cell death induced by QDs, which overlooks other aspects of QDs’ toxicity. Thus, our study aimed to provide another way by which QDs negatively impact cellular processes by investigating the possibility of protein structure and function modification upon direct interaction. Through shotgun proteomics, we identified a number of QD-binding proteins, which are functionally associated with essential cellular processes and components, such as transcription, translation, vesicular trafficking, and the actin cytoskeleton. Among these proteins, we chose to closely examine the interaction between quantum dots and actin, as actin is one of the most abundant proteins in cells and plays crucial roles in cellular processes and structural maintenance. We found that CdSe/ZnS QDs spontaneously bind to G-actin in vitro, causing a static quenching of G-actin’s intrinsic fluorescence. Furthermore, we found that this interaction favors the formation of a QD–actin complex with a binding ratio of 1:2.5. Finally, we also found that CdSe/ZnS QDs alter the secondary structure of G-actin, which may affect G-actin’s function and properties. Overall, our study provides an in-depth mechanistic examination of the impact of CdSe/ZnS QDs on G-actin, proposing that direct interaction is another aspect of QDs’ toxicity.

N-(1,3-dimethylbutyl)-N′phenyl-p-phenylenediamine, more commonly known as 6PPD, is a tire antiozonant used to prevent rubber oxidation and degradation. When 6PPD reacts with ozone, it becomes 6PPD-Quinone (6PPD-Q). Stormwater road runoff facilitates the transport of phenylenediamines (PPDs) into the environment. In recent years, 6PPD-Q has been identified as an acute environmental toxicant causing major disruptions to aquatic life. To aid in the growing body of knowledge on the mechanism of action of PPD and potentially support environmental regulations, this study aims to elucidate the toxic effects of 6PPD and 6PPD-Q in Saccharomyces cerevisiae. To accomplish this, a growth assay, RNA sequencing, mitochondrial staining, and RT-qPCR were performed. The results suggest that 6PPD and 6PPD-Q impact growth and gene regulation by dysregulating Complex III, IV, and V of the oxidative phosphorylation pathway. Additionally, 6PPD and 6PPD-Q are, seemingly, agglomerated at different pHs and in various media. The agglomeration of 6PPD-Q may inhibit cellular uptake, leading to fewer discernible toxic effects. Taken together, we can posit that 6PPD and 6PPD-Q both induce oxidative stress upon exposure to budding yeast, but 6PPD seems to be more toxic than 6PPD-Q.