A Plasmonic “Lid‐Off” Nanoplatform for Spatiotemporally Controlled PA/NIR‐II Dual‐Modal Imaging and Cuproptosis‐Based Synergistic Photothermal and Chemodynamic Therapy

ABSTRACT Current nanotheranostics are plagued by non‐target drug release and uncontrolled activation which compromise imaging fidelity and therapeutic precision. Herein, we report an origin‐regenerated Cu ₉ S ₈ @CH1055@Cu ₉ S ₈ nanocapsules (CCC NCs) that unlocks dual‐modal imaging‐guided trimodal therapy via a light‐triggered “lid‐off” mechanism. The dense outer Cu ₉ S ₈ shell tightly encapsulates the NIR‐II dye CH1055, ensuring its dormant state during systemic circulation. Upon the 1064 nm laser irradiation, localized surface plasmon resonance (LSPR) induces rapid photothermal disruption of the lid, thereby achieving a light‐gated “lid‐off” effect. This effect synchronously enables high‐contrast NIR‐II fluorescence/photoacoustic dual‐modal imaging and initiates on‐demand trimodal therapy integrating photothermal ablation, chemodynamic therapy, and cuproptosis. The single near infrared wavelength‐triggered design achieves remarkable suppression of Mouse prostate carcinoma (RM‐1) prostate tumor progression with no detectable systemic toxicity. Thereby, our work establishes the “lid‐off” nanoarchitecture as a robust platform for spatiotemporally precise, imaging‐guided multimodal cancer theranostics.