Macrophage membrane (MMs) camouflaged near-infrared (NIR) responsive bone defect area targeting nanocarrier delivery system (BTNDS) for rapid repair: promoting osteogenesis via phototherapy and modulating immunity

Bone defects remain a significant challenge in clinical orthopedics, but no targeted medication can solve these problems. Inspired by inflammatory targeting properties of macrophages, inflammatory microenvironment of bone defects was exploited to develop a multifunctional nanocarrier capable of targeting bone defects and promoting bone regeneration. The avidin-modified black phosphorus nanosheets (BP-Avidin, BP ) were combined with biotin-modified Icaritin (ICT-Biotin, ICT ) to synthesize Icaritin (ICT)-loaded black phosphorus nanosheets (BP ). BP was then coated with macrophage membranes (MMs) to obtain MMs-camouflaged BP (M@BP ). Herein, MMs allowed BP to target bone defects area, and BP accelerated the release of phosphate ions (PO ) and ICT when exposed to NIR irradiation. PO recruited calcium ions (Ca ) from the microenvironment to produce Ca (PO ) , and ICT increased the expression of osteogenesis-related proteins. Additionally, M@BP can decrease M1 polarization of macrophage and expression of pro-inflammatory factors to promote osteogenesis. According to the results, M@BP provided bone growth factor and bone repair material, modulated inflammatory microenvironment, and activated osteogenesis-related signaling pathways to promote bone regeneration. PTT could significantly enhance these effects. This strategy not only offers a solution to the challenging problem of drug-targeted delivery in bone defects but also expands the biomedical applications of MMs-camouflaged nanocarriers.