Biodegradable Fe-Doped Vanadium Disulfide Theranostic Nanosheets for Enhanced Sonodynamic/Chemodynamic Therapy

Sonodynamic therapy (SDT), a noninvasive and highly penetrating tumor therapy, which employs ultrasound and sonosensitizers, has attracted extensive attention because of its ability to treat deep tumors. However, many current sonosensitizers have drawbacks in phototoxicity and limited sonodynamic effect. Herein, as a novel kind of sonosensitizer, iron-doped vanadium disulfide nanosheets (Fe-VS₂ NSs) are constructed by a high-temperature organic-solution method and further modified with polyethylene glycol (PEG). With Fe doping, the sonodynamic effect of Fe-VS₂ NSs is greatly enhanced, owing to the prolonged electron-hole recombination time. Simultaneously, such Fe-VS₂-PEG NSs as a good Fenton agent can be utilized for chemodynamic therapy (CDT) by using the endogenous H₂O₂ in the tumor microenvironment (TME). Moreover, the multivalent Fe and V elements in the Fe-VS₂ NSs can consume glutathione to amplify the reactive oxygen species-induced oxidative stress by SDT and CDT. Utilizing the strong near-infrared optical absorbance and enhanced magnetic resonance (MR) contrast by Fe-VS₂ NSs, photoacoustic/MR biomodal imaging reveals a high accumulation of Fe-VS₂-PEG NSs in the tumor. The great tumor suppression effect is then achieved by the in vivo combined CDT&SDT treatment. Importantly, most of the injected Fe-VS₂-PEG NSs can be gradually decomposed and excreted from the mice, making them as safe sonosensitizers for cancer treatment. Our work highlights a new type of biodegradable sonosensitizer with the ability of regulating TME for applications in cancer theranostics.