Tumor-Adhesive Ru/Ca-Tannic Acid Network Enables Phosphate-Independent Calcification and Photothermal-Synergistic Therapy for Osteolytic Bone Metastasis.

Abstract

Osteolytic bone metastasis remains difficult to treat because effective tumor eradication and bone regeneration must be achieved simultaneously. Current calcification-based strategies are constrained by their reliance on exogenous phosphate, and poor integration with controllable therapeutic modalities. Herein, we report a tumor adhesive metal-phenolic network nanoplatform that enables phosphate-independent membrane biomineralization combined with photothermal amplification. The Ru/Ca-TA-ALN network, assembled from ruthenium ions (Ru3+), calcium ions (Ca2+), tannic acid (TA), and alendronate (ALN), co-integrates Ca2+ and phosphate-bearing moieties within a single coordination framework, allowing autonomous mineral deposition upon adhesion to tumor cell membranes. This membrane-confined calcified interface induced S-phase arrest, and impaired tumor viability. Under 1064 nm near-infrared (NIR) irradiation, Ru3+-mediated photothermal activation amplifies tumor cell apoptosis. Beyond tumor inhibition, the calcified nano-bio interface promoted osteogenic differentiation while suppressing osteoclastogenesis, shifting the bone microenvironment toward regeneration. In a murine breast cancer bone metastasis model, calcification-photothermal synergy significantly reduced tumor burden, mitigated bone destruction, and prolonged survival, while maintaining favorable biocompatibility. By transforming biomineralization into a controllable interfacial therapeutic modality, this work establishes a strategy that couples tumor suppression with bone reconstruction for metastatic bone disease.