A20 Silencing by Lipid Envelope-Type Nanoparticles Enhances the Efficiency of Lipopolysaccharide-Activated Dendritic Cells

作者：Warashina Shota; Nakamura Takashi; Harashima Hideyoshi^*

来源：Biological & Pharmaceutical Bulletin, 2011, 34(8): 1348-1351.

DOI：10.1248/bpb.34.1348

• non-viral delivery system
• short interference RNA
• dendritic cell
• A20
• multifunctional envelope-type nano device

In a previous report, we described the development of lipid envelope-type nanoparticles (MEND) modified with octaarginine (R8) and a pH-sensitive fusogenic peptide (GALA) for delivering short interference RNA (siRNA) to mouse dendritic cells (DCs). A20 was recently reported to be a negative regulator of the toll-like receptor and the tumor necrosis factor receptor signaling pathways. Although A20 would be expected to be a useful target for boosting the effects of adjuvants in DC immunotherapy, limited information is available regarding the use of A20-silenced DC by an original non-viral vector. In this study, we loaded anti-A20 siRNA into a MEND and investigated the gene knockdown activity in DC and the immunological functions of A20-silenced DC. The use of a MEND resulted in a significant A20 knockdown effect, and the A20-silenced DC resulted in an enhanced production of proinflammatory molecules, after lipopolysaccharide (LPS) stimulation. The expression of co-stimulatory molecules by LPS stimulation was also increased in the A20-silenced DC. The findings reported herein show that a MEND loaded with anti-A20 siRNA is a potent non-viral vector that has the ability to enhance the adjuvant effect of LPS in DC.

• 出版日期2011-8