HA-Modified R8-Based Bola-Amphiphile Nanocomplexes for Effective Improvement of siRNA Delivery Efficiency
Nan Jia, Jingjing Ma, Yan Gao, Haiyang Hu, Dawei Chen, Xiuli Zhao, Yue Yuan, Mingxi Qiao
Abstract
The development of new nonviral vectors with high transfection efficiency and low cyto-toxicity remains a great challenge in the field of small interfering RNA delivery. To address the challenge, we developed two cationic amphiphilic carriers, octa-arginine double-substituted (R8-bibola) and octa-arginine monosubstituted (R8-monobola), based on transmembrane peptide-octa-arginine (R8) for complexing siRNA (R8-bola/siRNA). To further improve the stability of the nanocomplexes and tumor targeting, HA-R8-bola/siRNA nanocomplexes were prepared by surface modification of R8-bola/siRNA with hyaluronic acid (HA). In vitro experiments showed that R8-bibola has better biocompatibility than R8-monobola, which effectively increased the cell uptake of siRNA and improved the Bcl-2 protein silencing efficiency. In vivo antitumor experiments confirmed that the HA-modified nanocomplexes effectively inhibited tumor growth by silencing Bcl-2 protein expression. The new bola-type nanoparticles provide a new strategy to improve the delivery efficiency of siRNA for tumor treatment.