Abstract 5519: Engineered protein nanocage for targeted delivery of siRNA to cancer cells

Considering the problems of small interfering RNA (siRNA) delivery using traditional viral and non-viral vehicles, a new siRNA delivery system to enhance efficiency and safety needs to be developed. Here we genetically engineered human ferritin based protein nanocage to simultaneously display various functional peptides on the surface of protein nanocage: cationic peptide to capture siRNA, tumor cell targeting and penetrating peptides, and enzymatically cleaved peptide to release siRNA inside tumor cell. In particular, we easily changed the tumor cell targeting peptide depending on target moiety [epidermal growth factor receptor or vimentin in this case] on the tumor cell surface. The polymerized siRNA (poly siRNA) tightly bound to the engineered protein nanocage and formed stable and condensed structure (poly siRNA-protein nanocage complex) without cytotoxicity problem. Furthermore, siRNAs in the condensed complex were effectively protected from endonuclease due to a shielding effect of protein nanocage. In the in vitro treatment of poly siRNA-protein nanocage complex, both of the tumor cell targeting and penetrating peptides were important for efficient delivery of siRNA, and the red fluorescent protein (RFP) expression in RFP-expressing tumor cells was notably suppressed by the delivered siRNA with the complementary sequence to RFP mRNA. It seems that the human ferritin-based protein nanocage is an efficient, stable, and safe tool for siRNA delivery, having a great potenti...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Cancer Chemistry Source Type: research