Cationic Polyaspartamide as siRNA delivery systems for down regulation of a proinflammatory cytokine

High-mobility group box 1 (HMGB1) protein, originally identified as a nuclear nonhistone protein with DNAbinding domains, can be secreted from cells and exert extracellular functions as a proinflammatory cytokine [1]. High levels of HMGB1 were found in inflammatory conditions of the respiratory tract such as asthma and chronic obstructive respiratory disease [2]. However, the pathogenetic role of HMGB1 in these diseases has not disclosed. In the last years, RNA interference has been shown as a powerful tool for post-transcriptional gene silencing [3]. The aim of this study was to evaluate the ability to two different polyaspartamide copolymers, bearing in the side chains, alone spermine groups (PHEA-Spm) or PEG/Spermine groups at the same time (PHEA-PEG-Spm), to promote the cell entry of a specific siRNA, able to down regulate by HMGB1, into H441 airway epithelial cells by the formation of nanocomplexes; moreover the efficiency of HMGB1 downregulation by PHEA copolymers/siRNA nanocomplexes was evaluated.