Liver cell specific targeting by the preS1 domain of hepatitis B virus surface antigen displayed on protein nanocages

Masaharu Murata,1,2 Sayoko Narahara,1,2 Kaori Umezaki,1 Riki Toita,1,2 Shigekazu Tabata,1 Jing Shu Piao,1 Kana Abe,1 Jeong-Hun Kang,3 Kenoki Ohuchida,1,4 Lin Cui,4 Makoto Hashizume1,21Department of Advanced Medical Initiatives, Faculty of Medical Science, Kyushu University, Fukuoka, Japan; 2Innovation Center for Medical Redox Navigation, Kyushu University, Fukuoka, Japan; 3Department of Biomedical Engineering, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan; 4Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanAbstract: Protein nanocages are self-organized complexes of oligomers whose three-dimensional architecture can been determined in detail. These structures possess nanoscale inner cavities into which a variety of molecules, including therapeutic or diagnostic agents, can be encapsulated. These properties yield these particles suitable for a new class of drug delivery carrier, or as a bioimaging reagent that might respond to biochemical signals in many different cellular processes. We report here the design, synthesis, and biological characterization of a hepatocyte-specific nanocage carrying small heat-shock protein. These nanoscale protein cages, with a targeting peptide composed of a preS1 derivative from the hepatitis B virus on their surfaces, were prepared by genetic engineering techniques. PreS1-carrying nanocages showed lower cytotoxicity and significantly higher specificity for human hepatocyte cell lines than other cell lines in vitro. These results suggested that small heat-shock protein-based nanocages present great potential for the development of effective targeted delivery of various agents to specific cells.Keywords: protein nanocages, drug delivery system, hepatocyte cell lines specific, hepatitis B virus