A self-luminescent and bone-targeted nanosystem for photodynamic therapy of breast cancer bone metastasis

Breast cancer constitutes the predominant malignancy occurring in women, with bone metastasis representing a major cause of treatment failure. Photodynamic therapy (PDT) has attracted considerable attention as a promising cancer treatment owing to its high spatiotemporal precision, minimal invasiveness, and limited systemic toxicity. Nevertheless, the shallow penetration of excitation light through biological tissues substantially compromises its therapeutic efficacy against deep-seated tumors. Here, we developed a bone-targeted self-luminescent nanosystem, CaO 2 /Ce6/CPPO@ZOL, for the treatment of breast cancer bone metastases through chemiluminescence resonance energy transfer (CRET)-driven PDT without external light irradiation. In this nanosystem, CaO 2 provided both H 2 O 2 and O 2 , while bis[3,4,6-trichloro-2-(pentyloxycarbonyl)phenyl] oxalate (CPPO) reacted with H 2 O 2 to generate a high-energy intermediate. The resulting chemical energy was transferred to chlorin e6 (Ce6) through CRET, thereby activating Ce6 to produce singlet oxygen in the presence of the generated O 2 . Zoledronic acid (ZOL) was introduced to enhance bone targeting and inhibit osteoclast-mediated bone resorption. The resulting nanosystem effectively generated reactive oxygen species and induced tumor cell death without external irradiation. Moreover, CaO 2 /Ce6/CPPO@ZOL exhibited favorable bone-targeting capability, suppressed tumor progression, and alleviated tumor-associated bone destruction. Collectively, this self-sustained CRET-based nanoplatform overcomes the dependence of conventional PDT on external light and integrates tumor eradication with the inhibition of bone resorption, providing a promising therapeutic strategy for breast cancer bone metastasis.