Iron-based magnetic nanocomplexes for combined chemodynamic and photothermal cancer therapy through enhanced ferroptosis

Chemodynamic therapy (CDT) guided by Fenton chemistry and iron-containing materials can induce ferroptosis as a prospective cancer treatment method, but the inefficient Fe 3+ /Fe 2+ conversion restricts the monotherapeutic performances. Here, an iron-based nanoplatform (Fe 3 O 4 -SRF@FeTA) including a magnetic core and a reductive film is developed for combined CDT and photothermal therapy (PTT) through ferroptosis augmentation. The inner iron oxide core serves as a photothermal transducer, a magnet-responsive module, and an iron reservoir for CDT. The coated Fe 3+ -tannic acid film (FeTA) provides extra iron and reductants for Fe 3+ /Fe 2+ conversion acceleration, and functions as a door keeper for the pH- and light-responsive release of the embedded ferroptosis inducer sorafenib (SRF). The in vitro results demonstrate that the iron-based nanocomplexes promote the production of lipid peroxide through the amplified Fenton activity, and downregulate glutathione involved in lipid peroxide repair system through the responsively released SRF. Upon accumulation in tumor by magnetic targeting and sequential laser irradiation locoregionally, Fe 3 O 4 -SRF@FeTA nanocomplexes present prominent in vivo anticancer efficacy by leveraging PTT and CDT-enhanced ferroptosis.