A microenvironment-responsive FePt probes for imaging-guided Fenton-enhanced radiotherapy of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) continues to be one of the most fatal malignancies with increasing morbidity, and potent therapeutics are urgently required given its insensitivity to traditional treatments. Here, we have developed a microenvironment-responsive FePt probes for the highly efficient Fenton-enhanced radiotherapy (FERT) of HCC. The selective release of Fe2+ in the acidic tumor microenvironment, but not in normal tissue, together with enhanced levels of hydrogen peroxide produced through the Pt radiosensitization effect, facilitates the generation of an enormous amount of hydroxyl radicals through the Fenton reaction, thereby extending the radiotherapeutic cascade and realizing a powerful therapeutic efficacy for HCC. Moreover, the “burst” release of Fe2+ contributes to the T2-to-T1 magnetic resonance imaging (MRI) switching effect, which informs the release of Fe2+, making imaging-guided cancer therapy feasible. This work not only breaks the bottleneck of traditional radiotherapy for HCC while minimally affecting normal tissues, but also provides a new strategy for FERT imaging guidance. Graphical Abstract: [Figure not available: see fulltext.].