Eradication of solid tumors by chemodynamic theranostics with H₂O₂-catalyzed hydroxyl radical burst

Activatable theranostics, integrating high diagnostic accuracy and significant therapeutic effect, holds great potential for personalized cancer treatments; however, their chemodynamic modality is rarely exploited. Herein, we report a new in situ activatable chemodynamic theranostics PAsc/Fe@Cy7QB to specifically recognize and eradicate cancer cells with H₂O₂-catalyzed hydroxyl radical (•OH) burst cascade. Methods: The nanomicelles PAsc/Fe@Cy7QB were constructed by self-assembly of acid-responsive copolymers incorporating ascorbates and acid-sensitive Schiff base-Fe²⁺ complexes as well as H₂O₂-responsive adjuvant Cy7QB. Results: Upon systematic delivery of PAsc/Fe@Cy7QB into cancer cells, the acidic microenvironment triggered disassembly of the nanomicelles. The released Fe²⁺ catalyzed the oxidation of ascorbate monoanion (AscH^-) to efficiently produce H₂O₂. The released H₂O₂, together with the endogenous H₂O₂, could be converted into highly active •OH via the Fenton reaction, resulting in enhanced Fe-mediated T₁ magnetic resonance imaging (MRI). The synchronously released Cy7QB was activated by H₂O₂ to produce a glutathione (GSH)-scavenger quinone methide to boost the •OH yield and recover the Cy7 dye for fluorescence and photoacoustic imaging. Conclusion: The biodegradable PAsc/Fe@Cy7QB designed for tumor-selective multimodal imaging and high therapeutic effect provides an exemplary paradigm for precise chemodynamic theranostic.