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

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 •SO₄ ^-/•OH radicals. The nanoreactor with an ultrahigh payload of free radical initiator is designed by encapsulating the Na₂S₂O₈ 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⁺/S₂O₈ ^{2 -} /Fe²⁺ and EG. Then a sequence of cascade reactions will be activated to efficiently generate •SO₄ ^- (Fe²⁺-catalyzed S₂O₈ ^{2 -} oxidation), proton (•SO₄ ^--catalyzed H₂O decomposition), and •OH (proton-intensified Fenton oxidation). Synchronously, the oxidation-generated Fe³⁺ will be in turn recovered into Fe²⁺ by excessive EG to circularly amplify •SO₄ ^-/•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.

cascade‐responsive; dual cycling amplification of •SO4−/•OH; tumour microenvironment.