Re-Arming the Immunological Radar: The Translational Landscape of Dendritic Cell-Centric Nanotherapeutics and...

For decades, survival rates in metastatic Osteosarcoma (OS) have starkly plateaued. The persistent failure of immune checkpoint blockade underscores a critical reality: the true therapeutic bottleneck is not merely exhausted T cells, but a profound upstream defect in antigen presentation by Dendritic cells (DCs). To overcome this, this review comprehensively outlines the translational landscape of DC-centric therapeutics in OS, tracing the paradigm shift from foundational ex vivo cellular vaccines to advanced in situ vaccination strategies. Specifically, we highlight how intelligent biomaterials and engineered endogenous vesicles bypass external manipulation to directly prime immunity within the tumor bed. Furthermore, we extensively evaluate state-of-the-art physicochemical nanomedicines-encompassing photothermal, sonodynamic, and metallo-immunologic modalities-engineered to force severe organellar stress, trigger robust immunogenic cell death, and actively reverse the spatial and metabolic paralysis of resident DCs. By coupling these interventions with targeted agents and adoptive cellular therapies, we map a synergistic roadmap for closing the cancer-immunity cycle. Despite remarkable preclinical successes, translating these ultra-complex nanoplatforms faces formidable scale-up challenges, and uncalibrated innate hyper-stimulation risks profound DC exhaustion. Moving forward, transitioning toward logic-gated, metabolically precise delivery systems is imperative to flawlessly repair the innate-adaptive immunity bridge and achieve durable OS eradication.