Engineered Hsp Protein Nanocages for siRNA Delivery

The efficient delivery of small interfering RNA (siRNA) to tumor cells still remains a great challenge. Of the various nanocarriers, protein nanocages have attracted extensive interest due to their unique structure and suitable characteristics derived from their proteinaceous nature. However, most reported protein nanocages that are developed are based on virus capsid proteins, which may raise safety concerns, including those related to gene mutation and carcinogenesis. The development of nonviral protein-based systems for siRNA delivery is greatly needed. In this study, a novel siRNA delivery system based on heat shock protein (Hsp) nanocages is developed by a genetic engineering method. The delivery system could condense siRNA into stable complexes and protect the condensed siRNA from degradation. A cellular uptake analysis shows that siRNA is introduced into tumor cells mediated by Hsp-R9 nanocages. Green fluorescent protein (GFP) expression in HeLa-EGFP cells is significantly downregulated by Hsp-R9/siRNA complexes. The results indicate that Hsp nanocages may be a good platform for siRNA delivery into tumor cells.