Precision nanomedicine for lung metastatic osteosarcoma: challenges, therapeutic strategies, and perspectives

Lung metastatic osteosarcoma (LM-OS) remains the leading cause of mortality in patients with osteosarcoma and is poorly controlled by current therapeutic regimens. The limited efficacy of conventional treatments is closely related to the complex biological features of metastatic lesions, including marked tumor heterogeneity, restrictive microenvironmental conditions, immune suppression, and emerging neural involvement within the lung niche. In recent years, nanomedicine has been increasingly explored as a mean to improve drug delivery and therapeutic effectiveness in LM-OS. A range of nanocarrier strategies has been developed to enhance metastatic targeting, modulate the tumor microenvironment, and integrate multiple therapeutic functions. In this review, we summarize recent advances in nanomedicine for LM-OS using a barrier-oriented and disease-matched framework. Representative nanocarrier platforms designed to address heterogeneity, immune clearance, limited metastatic accessibility, and tumor-nerve interactions are discussed, together with the underlying biological considerations. Current translational challenges, including safety, manufacturability, and limitations of existing preclinical models, are also examined, and perspectives on future directions for nanomedicine-based treatment of LM-OS are provided. By anchoring nanocarrier design to the biological logic of LM-OS, this review aims to provide a conceptual roadmap for developing clinically translatable precision nanotherapies.