Tumor-Adhesive Ru/Ca-Tannic Acid Network Enables Phosphate-Independent Calcification and Photothermal-Synergistic Therapy for Osteolytic Bone Metastasis.
TL;DR
A tumor adhesive metal-phenolic network nanoplatform that enables phosphate-independent membrane biomineralization combined with photothermal amplification and establishes a strategy that couples tumor suppression with bone reconstruction for metastatic bone disease.
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.