A light-controlled single-atom nanozyme hydrogels for glutathione depletion mediated low-dose radiotherapy

Due to the unique ability to mimic natural enzymes, single-atom nanoenzymes (SAE) have garnered significant attention and research in tumor therapy. However, their efficacy often faces challenges in terms of drug delivery methods, and the research regarding their applications in radiotherapy is scarce. Herein, we introduce a light-controlled SAE hydrogel platform (SH) for glutathione-depletion-mediated low-dose radiotherapy. The SH incorporates a Cu single-atom enzyme (CuSA), and upon irradiation with 1064 nm near-infrared light, the CuSA can convert light energy into heat, which in turn degrades the hydrogel, enabling the release of CuSA into tumor cells or tissues. The diffused CuSA not only can facilitate the conversion of H₂O₂into hydroxyl radicals (•OH), but also can effectively depletes cellular glutathione. This leads to increased sensitivity of tumor cells to radiotherapy, resulting in enhanced cytotoxicity even at low doses. The animal study results further confirmed the good tumor-killing efficacy of this SH system. To the best of our knowledge, this stands as the pioneering report on leveraging a single-atom enzyme for GSH depletion-mediated low-dose radiotherapy.