Hierarchically Multifunctional Fiber‐optic Theranostic Probe for Cancer Photothermal‐photodynamic Synergism

ABSTRACT Photodynamic therapy (PDT) is an FDA‐approved cancer treatment, yet its clinical efficacy is compromised by limited light penetration and hypoxia. Herein, we proposed a multifunctional fiber‐optic theranostic probe based on a spatially stratified functional multiplexing strategy: an inner sensing layer containing the oxygen‐sensitive probe (Ru(dpp)), an outer therapeutic layer loaded with the photosensitizer (ICG), and a thermally‐triggered oxygen generator (CaO ₂ @LA). Crucially, this layered design leverages wavelength‐dependent evanescent field properties to enable multi‐wavelength activation while spatially separating the sensor from the photosensitizer, thereby preventing signal crosstalk. Functionally, the incorporation of CaO ₂ @LA mitigates the hypoxia‐induced restriction on PDT, while the PTT‐PDT synergy achieves potent antitumor efficacy under mild hyperthermia, enhancing treatment safety. In vitro experiments demonstrated the probe's excellent dissolved oxygen (DO) sensing performance, featuring a high resolution of 0.12 mg/L, a rapid response time of 1 s, and efficient ROS generation. Subsequently, the probe demonstrated dual functionality in vivo within a murine model, allowing pointwise identification of intratumoral hypoxic heterogeneity through DO sensing, while achieving complete inhibition of tumor growth. This study provides a new paradigm for the functional integration and efficacy enhancement of fiber‐optic theranostics for in situ oncology, holding significant potential to advance the clinical translation of fiber‐mediated phototherapies.