Synthesis of mesoporous silica/polyglutamic acid peptide dendrimer with dual targeting and its application in dissolving thrombus.

With the frequent occurrence of thrombus diseases, thrombus has become a factor endangering human health. Nattokinase (NK) is a new generation of thrombolytic drug with efficient thrombolytic effect and no major side effects. However, it is easily inactivated in external environment due to its sensitivity, which is still a challenge for its generalized application. Herein, a mesoporous silica/polyglutamic acid peptide dendrimer (M-MSNs-G3 -RGD) nanoparticle was prepared to protect and transport NK. First, magnetic mesoporous silica nanoparticles (M-MSNs) were prepared as the core of the whole nanoparticle, then polyglutamic acid peptide dendrimer (G3 ) was bonded to form M-MSNs-G3 . At last, arginine-glycine-aspartic peptide (RGD) was grafted onto the M-MSNs-G3 to obtain M-MSNs-G3 -RGD. The physical and chemical characteristics and biological toxicity of M-MSNs-G3 -RGD were studied. Thrombus-targeting nanocomposites M-MSNs-G3 -RGD/NK were prepared by loading the thrombolytic drug NK via electrostatic interaction. In vitro and in vivo targeted thrombolytic experiments showed that the nanoparticles exhibited significant thrombolysis ability. These results suggested the potential application of M-MSNs-G3 -RGD/NK in dual targeted thrombolysis.