Nanotechnology-Driven Strategies in Osteosarcoma Advances in Treatment: Immunotherapy and Drug Delivery

Osteosarcoma (OS), the most prevalent primary malignant bone tumor, exhibits highly aggressive and metastatic potential, accounting approximately 56% of all primary malignant bone malignancies. While neoadjuvant chemotherapy with surgery remains standard, challenges persist: suboptimal margins, non-specific drug biodistribution, and systemic toxicity. Nanomaterial engineering offers transformative multifunctional platforms, integrating biomimetic targeting, stimuli-responsive release, and theranostics to enhance tumor penetration and reduce off-target effects. Immunotherapy combats OS by activating antitumor immunity, reprogramming the immunosuppressive tumor microenvironment (TME), and synergizing with checkpoint inhibitors/cell therapies. Ligand-functionalized nanocarriers significantly improve chemotherapeutic bioavailability and targeting. This review systematically explores the dual role of nanoplatforms in osteosarcoma therapeutics: (1) immunotherapy via TME reprogramming and (2) precision oncology through advanced drug delivery paradigms, providing critical insights into their translational potential for overcoming current therapeutic bottlenecks and ultimately improving clinical outcomes for OS patients.