Nanoparticle dynamics in the presence and absence of a cellular uptake altering chemical

The far-reaching applications of nanoparticles (NPs) in drug delivery, medical imaging, diagnostics, and therapeutics have led to an increased potential for interfacing with a diverse range of biological environments. While metallic NPs such as copper NPs have been explored for their antimicrobial and catalytic properties, they have been shown to induce undesirable toxic effects. Nonetheless, bio modulators may be employed to control this cytotoxicity. Dynasore is a dynamin GTPase inhibitor that has been shown to rapidly and reversibly block clathrin dependent endocytic traffic within minutes of application. Here, we demonstrate that Dynasore can chemically bio-modulate the toxic effects of copper nanoparticles (Cu NPs), but not through reducing Cu NP internalization. In fact, Dynasore seems to possess secondary effects that have been unreported to date. We propose and test three potential mechanisms of cytotoxicity modulation: 1) through changes in agglomeration pattern, 2) through potential quenching of reactive oxygen species (ROS), and 3) through Cu+2 ion chelation. These results have far-reaching implications for understanding the complex interactions that occur at the interface of NPs in biological environments, especially during mechanistic chemical modification strategies.