H2S‐Scavenged and Activated Iron Oxide‐Hydroxide Nanospindles for MRI‐Guided Photothermal Therapy and Ferroptosis in Colon Cancer

Abstract Overproduced hydrogen sulfide (H 2 S) is of vital importance for the progress of colon cancer and promotes cancer cellular proliferation. Devising pharmacological nanomaterials for tumor‐specific H 2 S activation will be significant for precise colon cancer treatment. Herein, a biocompatible fusiform iron oxide‐hydroxide nanospindles (FeOOH NSs) nanosystem for magnetic resonance imaging (MRI), ferroptosis, and H 2 S based cascade reaction‐enhanced combinational colon cancer treatment is developed. The FeOOH NSs can effectively scavenge endogenous H 2 S via the reduction reaction to prohibit the growth of CT26 colon cancer. The cascade produced FeS driven by overexpressed H 2 S exhibits near‐infrared‐triggered photothermal therapy capability and Fe 2+ ‐mediated ferroptosis functionality. Meanwhile, the as‐prepared FeOOH NSs can light up tumor tissues as a potent MRI contrast agent. Additionally, FeOOH NSs present desirable biosafety in a murine model for up to three months and avoid any long‐term toxicity. Furthermore, it is found that these H 2 S‐responsible nanotheranostics do not cause any cure effects on other cancer types, such as 4T1 breast cancer. Overall, the findings illustrate that the biocompatible FeOOH NSs can be successfully employed as a theranostic for specifically treating colon cancer, which may promote the clinical translation and development of H 2 S‐responsive nanoplatforms.