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 reative oxygen species (ROS)-generating efficiency due to tumour hypoxia, strict Fenton reaction conditions, and un-sustainable mono-catalytic reaction. To fight against these issues, a tumour–microenvironment-responsive yolk–shell nanoreactor is developed to realize the high-efficiency, selective, and sustainable dynamic therapy via cascade-responsive dual cycling amplification of •SO4−/•OH radicals.

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 •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+/S2O82/Fe2+ and EG. Then a sequence of cascade reactions will be activated to efficiently generate •SO4 (Fe2+-catalyzed S2O82 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.

Author list:

Yang Li†, Jinyan Lin†, Yueyang He, Kaiyuan Wang, Cailin Huang, Ruifeng Zhang, Xiaolong Liu*

How to cite:

Y. Li, J. Lin, Y. He, K. Wang, C. Huang, R. Zhang, X. Liu, Exploration 2023, 20230054.
https://doi.org/10.1002/EXP.20230054