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 center dot SO4-/center dot 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+/S2O82(-)/Fe2+ and EG. Then a sequence of cascade reactions will be activated to efficiently generate center dot SO4- (Fe2+-catalyzed S2O82(-) oxidation), proton (center dot SO4--catalyzed H2O decomposition), and center dot OH (proton-intensified Fenton oxidation). Synchronously, the oxidation-generated Fe3+ will be in turn recovered into Fe2+ by excessive EG to circularly amplify center dot SO4-/center dot 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.