NIR-II Luminescent and Multi-Responsive Rare Earth Nanocrystals for Improved Chemodynamic Therapy

mediated Fenton reaction can amplify intracellular oxidative stress by producing toxic center dot OH. However, the high-dose need for Fe2+ delivery in tumors and its significant cytotoxicity to normal tissues set a challenge. Therefore, a controllable delivery to activate the Fenton reaction and enhance Fe2+ tumor accumulation has become an approach to solve this conflict. Herein, we report a rare-earthtechniques and DNA nanotechnology to realize programmable Fe2+ delivery. Ferrocenes, the source of Fe2+, are modified on the surface of RENCs through pH-responsive DNAs, which are further shielded by a PEG layer to elongate blood circulation and "turn off" the cytotoxicity of ferrocene. The up-/down-conversion dual-mode emissions of RENCs endow the delivery system with both capabilities of diagnosis and delivery control. The down-conversion NIR-II fluorescence can locate tumors. Consequently, upconversion UV light spatiotemporally activates the catalytic activity of Fe2+ by shedding off the protective PEG layer. The exposed ferrocene-DNAs not only can "turn on" Fenton catalytic activity but also respond to tumor acidity, driving cross-linking and enhanced Fe2+ enrichment in tumors by 4.5-fold. Accordingly, this novel design concept will be inspiring for developing CDT nanomedicines in the future.