Tumour‐microenvironment‐responsive Na₂S₂O₈ nanocrystals encapsulated in hollow organosilica–metal–phenolic networks for cycling persistent tumour‐dynamic therapy

Abstract Traditional tumour‐dynamic therapy still inevitably faces the critical challenge of limited reactive oxygen species (ROS)‐generating efficiency due to tumour hypoxia, extreme pH condition for Fenton reaction, and unsustainable mono‐catalytic reaction. To fight against these issues, we skilfully develop a tumour‐microenvironment‐driven yolk‐shell nanoreactor to realize the high‐efficiency persistent dynamic therapy via cascade‐responsive dual cycling amplification of •SO 4 − /•OH radicals. The nanoreactor with an ultrahigh payload of free radical initiator is designed by encapsulating the Na 2 S 2 O 8 nanocrystals into hollow tetra‐sulphide‐introduced mesoporous silica (HTSMS) and afterward enclosed by epigallocatechin gallate (EG)‐Fe(II) cross‐linking. Within the tumour microenvironment, the intracellular glutathione (GSH) can trigger the tetra‐sulphide cleavage of nanoreactors to explosively release Na + /S 2 O 8 2 − /Fe 2+ and EG. Then a sequence of cascade reactions will be activated to efficiently generate •SO 4 − (Fe 2+ ‐catalyzed S 2 O 8 2 − oxidation), proton (•SO 4 − ‐catalyzed H 2 O decomposition), and •OH (proton‐intensified Fenton oxidation). Synchronously, the oxidation‐generated Fe 3+ will be in turn recovered into Fe 2+ by excessive EG to circularly amplify •SO 4 − /•OH radicals. The nanoreactors can also disrupt the intracellular osmolarity homeostasis by Na + overload and weaken the ROS‐scavenging systems by GSH exhaustion to further amplify oxidative stress. Our yolk–shell nanoreactors can efficiently eradicate tumours via multiple oxidative stress amplification, which will provide a perspective to explore dynamic therapy.