Inhibition of Osteoclasts in Multiple Myeloma by Reactive Oxygen Species Responsive Alendronate Liposomes

Abstract

In recent years, nanomedicine delivery systems have shown unique advantages in treating various diseases, especially for tumor diseases. Our study synthesized reactive oxygen species (ROS) responsive phospholipid DSPE-TK-PEG2000 and constructed ROS responsive liposomes loaded with alendronate using thin-film hydration method. Dynamic light scattering (DLS) showed that the liposomes had good nanoparticle size and polydispersity index (PDI), negative zeta potential and transmission electron microscope (TEM) also showed that the liposomes had a spherical appearance and nanoscale size. In vitro release experiments confirmed their ROS responsive release ability. Through lyophilization procedure and resconstituted the liposomes, and placing at room temperature for 8 days, we found no significant changes in the appearance and DLS of the material, proving that alendronate liposomes are relatively stable. Bone marrow derived macrophages (BMMs) cytotoxicity experiments have shown that alendronate liposomes did not exhibit cytotoxicity at concentrations below 10−5 M. Meanwhile, Western blotting suggested that drug loaded liposomes could inhibit osteoclast associated proteins. The above studies indicated the potential of ROS responsive alendronate liposomes in inhibiting osteoclasts in multiple myeloma.