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

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 (CaO₂@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 CaO₂@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.