Controllable Gold Nanocluster–Emulsion Interface for Direct Cell Penetration and Photothermal Killing

Abstract In the view of their ability to be uptaken by cells, colloidal particles can exert diverse physiological effects and are promising vehicles for the intracellular delivery of biologically active substances. Given that the modulation of biomaterial interfaces greatly facilitates the prediction and control of the corresponding cellular responses, the interfacial behavior of hydrophobic dye‐modified gold (Au) nanoclusters (Au NCs) is rationally designed to develop Au NC‐containing emulsions and control their biointerfacial interactions with cell membranes. The observed biological performance is indicative of a physical penetration mechanism. The amphiphilic Au NCs decrease the interfacial energy of two immiscible liquids and hinder droplet coalescence to facilitate the formation of emulsions thermodynamically stabilized by dipole–dipole and hydrophobic interactions. Moreover, the amphiphilic Au NCs are localized on the emulsion droplet surface and form segregated interfacial microdomains that adapt to the membrane structure and facilitate the traverse of the emulsions across the cell membrane via direct penetration. Fast penetration coupled with excellent photophysical performance endows the emulsions with multifluorescence tracing and efficient photothermal killing capabilities. The successful change of the interaction mode between NCs and biological objects and the provision of a universal formulation to modulate biointerfacial interactions are expected to inspire new bioapplications.