Analysis of the Heterogeneity of the Immune Microenvironment of Bone Metastases and New Strategies of Nanotechnology intervention

Abstract

Bone metastases constitute one of the most severe complications in patients with advanced malignancies. Conventional treatment approaches face significant limitations: surgical intervention carries a high risk of recurrence; radiotherapy and chemotherapy often cause myelosuppression; and anti-resorptive agents provide only limited control over tumor progression. Although immunotherapy has achieved remarkable success in various solid tumors in recent years, its therapeutic impact on bone metastases remains limited. This limitation is largely attributed to the distinct immunosuppressive microenvironment within bone lesions, which is marked by (1) a substantial decline in both the quantity and functional activity of effector immune cells, coupled with an abnormal accumulation of immunosuppressive cell populations, and (2) the formation of a vicious cycle of "tumor growth-bone metabolic imbalance-immune suppression," driven by complex signaling interactions among osteoblasts, osteoclasts, and tumor cells. Recently, nanomaterials have emerged as promising therapeutic platforms due to their precise targeting and delivery capacity, inherent immune-stimulatory properties, and potential to restore bone homeostasis. Nonetheless, translating nanoplatforms into clinical practice for skeletal lesions remains a formidable challenge. This review highlights how specialized organic-inorganic hybrids and biomimetic nanoplatforms have achieved the most significant microenvironment remodeling and osteolytic inhibition within intraosseous murine models. Ultimately, we provide an actionable roadmap detailing how integrating multi-omics precision profiles and temporal programmable delivery can bridge the gap between preclinical nanomedicine and clinical oncological translation.