Targeted delivery of liver X receptor agonist to inhibit neointimal hyperplasia by differentially regulating cell behaviors

Restenosis induced by neointimal hyperplasia is one of the key reasons limiting the long-term success of cardiovascular interventional therapy. However, it remains a serious challenge to completely overcome restenosis because of the dilemma of simultaneously activating human umbilical vein endothelial cells (HUVECs) and inhibiting human aortic smooth muscle cells (HASMCs). Herein, we developed a targeted nanomedicine encapsulating the liver X receptor (LXR) agonist, T0901317, for differentially regulating the behaviors of HUVECs and HASMCs. The stimulatory effect on HUVEC proliferation/migration and the inhibitory effect on HASMC proliferation/migration were confirmed in vitro, respectively. In the co-culture system, the competitiveness of HUVECs over HASMCs was notably improved after being treated with T0901317-loaded liposomes. Compared to free T0901317 and non-targeted liposomes, the type IV collagen (Col-IV) targeted liposomes could accumulate in the vascular injured area more effectively and inhibit neointimal hyperplasia in a balloon-induced rat carotid artery injury model. Therefore, targeted delivery of LXR agonist might be a very promising therapeutic strategy for anti-restenosis therapy.