Two-Dimensional Biodegradable <scp>l</scp>-Cysteine-Iodine Nanosheets for Computed Tomography-Guided Cancer Synergistic Sonodynamic Therapy and Chemotherapy

Biodegradable versatile inorganic nanomaterials are highly desirable in the field of nanomedicine. Here, for the first time, we report a kind of novel two-dimensional biodegradable l-cysteine-iodine (l-Cys-I) nanosheet with high computed tomography (CT) imaging ability and sonosensitization efficacy. Such l-Cys-I nanosheets consist of iodine molecules and l-Cys, where the iodine molecules are coordinated and stabilized by l-Cys and cross-linked to form nanosheets through disulfide bonds. The large and convenient functional surface is further modified with targeting moieties DSPE-PEG-RGD and cancer drug doxorubicin (DOX) to construct a nanotheranostic nanoplatform (CIRD). Under ultrasound irradiation, the CIRD nanosheets assist in tremendous reactive oxygen species generation and controllable DOX release, leading to remarkable anticancer performance both in vitro and in vivo due to the synergistic sonodynamic therapy (SDT) and chemotherapy. Our results validate that the CIRD nanosheets enable effective body excretion and negligible systemic toxicity owing to the biodegradation properties. The CIRD nanosheets, with biodegradability, biocompatibility, and versatility, hold great promise in nanotheranostics.