In Situ Synthesis of FeOCl in Hollow Dendritic Mesoporous Organosilicon for Ascorbic Acid-Enhanced and MR Imaging-Guided Chemodynamic Therapy in Neutral pH Conditions

Chemodynamic therapy (CDT) based on the Fenton reactionis a promising strategy for nonlight cancer treatment. However, the traditional Fenton reaction is only efficient in strongly acidic conditions (pH = 2-4),resulting in the limited curative effect in a weakly acidic tumor microenvironment(TME). Herein, we first developed a simple in situ growth method toconfine FeOCl nanosheets into hollow dendritic mesoporous organosilicon(H-DMOS) nanoparticles to obtain FeOCl@H-DMOS nanospheres. Ascorbicacid (AA) was then absorbed on the nanosystem as a H2O2 prodrug and,meanwhile, was used for the regeneration of Fentons reagent for Fe2+. Finally,poly(ethylene glycol) (PEG) was coated on FeOCl@H-DMOS-AA toenhance the permeability and retention (EPR) effect in tumor tissue. Theas-fabricated FeOCl@H-DMOS-AA/PEG can generate a large amount of highly toxic hydroxyl radicals ((OH)-O-center dot) by catalyzing H2O2 even in neutral pH conditions with the help of AA. As a result, the effect of CDT has been markedly enhanced by the increased amount of H2O2 and the efficient Fenton reaction in mild acidic TME, which can remove almost all of the tumors in mice. In addition, FeOCl also endows the nanosystem with T-2-weighted MR imaging capability (r(2) = 34.08 mM(-1) s(-1)), thus realizing the imaging-guided cancer therapy.All in all, our study may contribute a new direction and may have a bright future for enhanced CDT with a neutral pH range.