By taking advantage of the efficient Forster resonance energy transfer (FRET) between near-infrared (NIR)-responsive lanthanide-doped upconversion nanoparticles (UCNPs) and Fenton reagent ferrocenyl compounds (Fc), a series of Fc-UCNPs was designed by functionalizing NaYF 4 :Yb,Tm nanoparticles with Fc1−Fc5 via surfacecoordination chemistry. Fc-UCNP-Lipo nanosystems were then constructed by encapsulating Fc-UCNP inside liposomes for efficient delivery. Fc-UCNP can effectively release •OH via a NIR-promoted Fenton-like reaction. In vitro and in vivo studies of Fc1-UCNP-Lipo confirmed the preferential accumulation in a tumor site followed by an enhanced uptake of cancer cells. After cellular internalization, the released Fc1-UCNP can effectively promote •OH generation for tumor growth suppression. Such a Fc1-UCNP-Lipo nanosystem exhibits advantages such as easy fabrication, low drug dosage, and no ferrous ion release.

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