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
Peng Xue, Zhiyong Chang, Hao Chen, Hongzhong Xi, Xiaoxue Tan, Shuai He, Haishi Qiao, Xiaohong Jiang, Xin Liu, Bin Du
Abstract
Abstract 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