Neutrophil-lifecycle-inspired nanoplatform for the treatment of lung cancer bone metastasis.

Difficulty in achieving effective drug concentration in bone metastasis has been a major challenge for tumor treatment because of the complex physiological environment of bone. Existing bone-targeting nanoparticles exhibit insufficient active targeting capability which relies on the binding of bisphosphonates and calcium. Hence, based on the homing property of aged neutrophils, we construct a C-X-C motif chemokine receptor 4 (CXCR4) targeting peptide, E5 peptide, modified liposome delivery system (D_E5-LPs) loaded with doxorubicin (DOX) that enables specific anchorage of nanoparticles to CXCR4hi aged neutrophils and enhances drug accumulation in bone metastasis. The D_E5-LPs effectively inhibit tumor growth and reduce systemic toxicity induced by chemotherapeutic drugs in a murine model of lung adenocarcinoma bone metastasis. Collectively, this study presents an effective strategy for bone-targeting drug delivery and expands therapeutic strategies for bone-related diseases.