Liposomal multimodal theranostics for bone disorders: from rational responsive delivery and biomimetic strategies to clinical translation

Bone and bone-related disorders remain difficult to diagnose and treat because of the dense mineralized matrix, limited vascular perfusion, complex pathological microenvironment, and insufficient site-specific accumulation of conventional agents. Liposomes, as biocompatible vesicular nanocarriers capable of loading therapeutic, genetic, and imaging cargos, have emerged as versatile platforms for bone-oriented theranostics. In contrast to previous reviews mainly focusing on general liposomal drug delivery or individual skeletal diseases, this review provides an integrated perspective on liposomal multimodal theranostics for bone disorders, emphasizing responsive delivery, diagnostic imaging, biomimetic engineering, and clinical translation. We first summarize the structural features, classification, and functional modification of liposomes, including bone-targeting ligands, stimuli-responsive release, membrane-penetrating delivery, and biomimetic designs. We then discuss their diagnostic and therapeutic applications in osteomyelitis, joint tuberculosis, rheumatoid arthritis, osteoarthritis, osteoporosis, bone defects, fracture nonunion, bone tumors, and spinal cord injury, with particular attention to radiolabeled liposomes, fluorescent probes, imaging-guided therapy, and microenvironment-responsive systems. Moreover, biomimetic liposomes, such as cell membrane-camouflaged, macrophage- or erythrocyte membrane-engineered, membrane-fusion-inspired, and organelle-delivering liposomal systems, are highlighted for their roles in immune evasion, lesion targeting, barrier penetration, and intercellular delivery. Finally, we discuss key translational challenges, including manufacturing reproducibility, stability, biosafety, immune responses, disease-model relevance, and clinical evaluation. This review aims to provide a rational framework for developing responsive and biomimetic liposomal theranostic systems for bone-related diseases.