The promoted delivery of RRM2 siRNA to vascular smooth muscle cells through liposome-polycation-DNA complex conjugated with cell penetrating peptides

Peripheral vascular disease (PVD) is a prevalent vascular disease that affect a large number of patients. The establishment of optimal treatments to mitigate the intimal hyperplasia (IH)-induced restenosis would help relieve the health burden of the PVD. Ribonucleotide reductase M2 (RRM2) is critical to cellular migration and proliferation. We have previously demonstrated that suppression of RRM2 expression could substantially inhibit hepatocellular carcinoma cell proliferation and migration. We hereby developed RRM2 small interfering RNA (siRNA)-loaded cell penetrating peptides-conjugated liposome-polycation-DNA complex (LPD) (RRM2-CLPD), aiming to inhibit the migration and proliferation of vascular smooth muscle cells (VSMCs) crucial for IH. RRM2-CLPD is of a small size (∼150 nm) and high siRNA encapsulation efficiency (∼90%). Further, we demonstrated that RRM2-CLPD could significantly inhibited RRM2 gene and protein expression by ∼80%. Notably, RRM2-CLPD was able to effectively bind to VSMCs, resulting in significant cellular proliferation and migration inhibition. Taken together, RRM2-CLPD represent a very promising treatment for IH.