Comparative study of nanostructured carriers of calcium phosphate and magnesium phosphate loaded with SRT1720 for the protection of H 2 O 2 -induced senescent endothelium.

Nanostructured calcium phosphate (CaP) and magnesium phosphate (MgP) are promising for the application as the nanocarriers in drug delivery. However, the difference between CaP and MgP nanocarriers in drug delivery is rarely investigated. In this work, we comparatively investigated nanostructured CaP, MgP and calcium magnesium phosphate (CMP) for the delivery of SRT1720, which is a silent information regulator (SIRT1) specific activator with pro-angiogenic and anti-aging properties in response to hydrogen peroxide (H2 O2 )-induced endothelial senescence. The protection of SRT1720-loaded CaP nanospheres, MgP nanosheets and CMP microspheres on the H2 O2 -induced senescent endothelium was examined by using human umbilical vein endothelial cells (HUVECs), demonstrating the improved cell viability, anti-aging, tube formation and migration. In addition, the SRT1720-loaded CaP nanospheres, MgP nanosheets and CMP microspheres can rescue the impaired angiogenic potential of HUVECs via activation of Akt/eNOS/VEGF pathway. The SRT1720-loaded MgP nanosheets and CMP microspheres have a similar protective effect compared with the pure SRT1720, while the SRT1720-loaded CaP nanospheres decrease the protective capability of SRT1720. These results lead us to figure out both MgP nanosheets and CMP microspheres are suitable and effective delivery for SRT1720 and this system can be further applied in vivo treatment.