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 Avi ) were combined with biotin-modified Icaritin (ICT-Biotin, ICT Bio ) to synthesize Icaritin (ICT)-loaded black phosphorus nanosheets (BP ICT ). BP ICT was then coated with macrophage membranes (MMs) to obtain MMs-camouflaged BP ICT (M@BP ICT ). Herein, MMs allowed BP ICT to target bone defects area, and BP ICT accelerated the release of phosphate ions (PO 4 3? ) and ICT when exposed to NIR irradiation. PO 4 3? recruited calcium ions (Ca 2+ ) from the microenvironment to produce Ca 3 (PO 4 ) 2 , and ICT increased the expression of osteogenesis-related proteins. Additionally, M@BP ICT can decrease M1 polarization of macrophage and expression of pro-inflammatory factors to promote osteogenesis. According to the results, M@BP ICT 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. Graphical Abstract

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