Microenvironment-Responsive Targeted Nanomedicine for a Collaborative Integration of Tumor Theranostics and Bone Defect Repair

Abstract

Despite advancements in breast cancer treatment, bone metastases remain a significant concern for advanced breast cancer patients. Current theranostics strategies face challenges in integrating tumor theranostics and bone formation. Herein, this work develops an activatable targeted nanomedicine AuMnCO@BSA-N₃ (AMCBN) to enable a novel collaborative integration of second near-infrared (NIR-II) fluorescence imaging guided precise theranostics for breast cancer bone metastases and osteogenic microenvironment remolding. This strategy employs a chemical coordination between noble metal complex and metal carbonyl (MnCO), with surface modification of azide groups to enhance tumor affinity through passive and active targeting. The initiated respondent behavior of AMCBN by tumor microenvironment accelerate the degradation of coordinated MnCO, resulting in a rapid release of multifunctional agents for efficient chemodynamic therapy (CDT)/gas synergistic therapy. Meanwhile, the exceptional bone-binding properties enable the efficient and controlled release of Mn²⁺ ions and carbon monoxide (CO) in the bone microenvironment, thereby facilitating the expression of osteogenesis-related proteins and establishing a novel synchronous theranostics process for tumor-bone repair.

Keywords: NIR‐II fluorescence imaging; breast cancer bone metastases; chemodynamic therapy; gas therapy; osteogenic microenvironment remolding.