Targeting Hyperglycemic Bone Pre‐Metastatic Niche for Breast Cancer Bone Metastasis Therapy

Abstract Bone is the most common site of breast cancer metastasis, yet understanding the intricate mechanisms and potential therapeutic targets remains nascent. Here it is reported that breast cancer establishes a hyperglycemic bone pre‐metastatic niche before migrating to bone tissue and further enhances glucose metabolism following metastatic colonization. An intervention strategy is subsequently proposed targeting glucose metabolism utilizing a biomimetic‐engineered enzyme‐based nanoplatform. This platform's membrane shielding reduces the interaction between engineered glucose oxidase and circulating glucose, while the engineered enzyme specifically targets glucose metabolism, enabling self‐amplifying starvation combined with selective chemotherapy. Such precision can precisely inhibit breast cancer bone metastases and block distal tumor dissemination. This study provides novel insights into the role of glucose metabolism in the pre‐metastatic niche and presents a proof‐of‐concept for metabolic‐targeted strategies in breast cancer bone metastasis treatment. This approach holds significant promise for improving therapeutic outcomes in metastatic breast cancer by targeting the metabolic vulnerabilities of the bone microenvironment and halting systemic tumor spread.