Platelet-derived porous nanomotor for thrombus therapy
Wan, MM (Wan, Mimi)[ 1 ]*（万密密）; Wang, Q (Wang, Qi)[ 1,2 ] ; Wang, RL (Wang, Rongliang)[ 3 ] ; Wu, R (Wu, Rui)[ 3 ] ; Li, T (Li, Ting)[ 1 ] ; Fang, D (Fang, Dan)[ 1 ] ; Huang, YY (Huang, Yangyang)[ 1 ] ; Yu, YQ (Yu, Yueqi)[ 1 ] ; Fang, LY (Fang, Leyi)[ 1 ] ; Wang, XW (Wang, Xingwen)[ 1 ] ; Zhang, YH (Zhang, Yinghua)[ 1 ] ; Miao, ZY (Miao, Zhuoyue)[ 1 ] ; Zhao, B (Zhao, Bo)[ 1 ] ; Wang, FH (Wang, Fenghe)[ 2 ] ; Mao, C (Mao, Chun)[ 1 ]*（毛春）; Jiang, Q (Jiang, Qing)[ 3 ] ; Xu, XQ (Xu, Xingquan)[ 3 ] ; Shi, DQ (Shi, Dongquan)[ 3 ]*
[ 1 ]Nanjing Normal Univ, Natl & Local Joint Engn Res Ctr Biomed Funct Mat, Sch Chem & Mat Sci, Nanjing 210023, Peoples R China
[ 2 ]Nanjing Normal Univ, Sch Environm, Jiangsu Prov Key Lab Environm Engn, Nanjing 210023, Peoples R China
[ 3 ]Nanjing Univ, Dept Sports Med & Adult Reconstruct Surg, Nanjing Drum Tower Hosp, Med Sch,Affiliated Hosp, Nanjing 210008, Peoples R China
The treatment difficulties of venous thrombosis include short half-life, low utilization, and poor penetration of drugs at thrombus site. Here, we develop one kind of mesoporous/macroporous silica/platinum nanomotors with platelet membrane (PM) modification (MMNM/PM) for sequentially targeting delivery of thrombolytic and anticoagulant drugs for thrombus treatment. Regulated by the special proteins on PM, the nanomotors target the thrombus site and then PM can be ruptured under near-infrared (NIR) irradiation to achieve desirable sequential drug release, including rapid release of thrombolytic urokinase (3 hours) and slow release of anticoagulant heparin (>20 days). Meantime, the motion ability of nanomotors under NIR irradiation can effectively promote them to penetrate deeply in thrombus site to enhance retention ratio. The in vitro and in vivo evaluation results confirm that the synergistic effect of targeting ability from PM and motion ability from nanomotors can notably enhance the thrombolysis effect in both static/dynamic thrombus and rat model.