Self‐Assembled Metal–Phenolic Networks on Emulsions as Low‐Fouling and pH‐Responsive Particles

Abstract Interfacial self‐assembly is a powerful organizational force for fabricating functional nanomaterials, including nanocarriers, for imaging and drug delivery. Herein, the interfacial self‐assembly of pH‐responsive metal–phenolic networks (MPNs) on the liquid–liquid interface of oil‐in‐water emulsions is reported. Oleic acid emulsions of 100–250 nm in diameter are generated by ultrasonication, to which poly(ethylene glycol) (PEG)‐based polyphenolic ligands are assembled with simultaneous crosslinking by metal ions, thus forming an interfacial MPN. PEG provides a protective barrier on the emulsion phase and renders the emulsion low fouling. The MPN‐coated emulsions have a similar size and dispersity, but an enhanced stability when compared with the uncoated emulsions, and exhibit a low cell association in vitro, a blood circulation half‐life of ≈50 min in vivo, and are nontoxic to healthy mice. Furthermore, a model anticancer drug, doxorubicin, can be encapsulated within the emulsion phase at a high loading capacity (≈5 fg of doxorubicin per emulsion particle). The MPN coating imparts pH‐responsiveness to the drug‐loaded emulsions, leading to drug release at cell internalization pH and a potent cell cytotoxicity. The results highlight a straightforward strategy for the interfacial nanofabrication of pH‐responsive emulsion–MPN systems with potential use in biomedical applications.