title: Design and Function of Engineered Protein Nanocages as a Drug Delivery System for Targeting Pancreatic Cancer Cells via Neuropilin-1.
abstract: We describe the development of neuropilin 1-binding peptide (iRGD)-nanocages that specifically target human pancreatic cancer cells in which an iRGD is joined to the surface of naturally occurring heat shock protein (HSP) cages. Using a genetic engineering approach, the iRGD domain was joined to the C-terminal region of the HSP cage using flexible linker moieties. The characteristics of the interdomain linkages between the nanocage and the iRGD domain play an important role in the specificity and affinity of the iRGD-nanocages for their target cells. An engineered L30-iRGD-nanocage with 30 amino acid linkers, (GGS)10, showed greater binding affinity for pancreatic cancer cells relative to that of other linkers. Furthermore, a moderately hydrophobic anticancer drug, OSU03012, was successfully incorporated into the L30-iRGD-nanocage by heating the mixture. The OSU03012-loaded L30-iRGD-nanocage induced cell death of pancreatic cancer cells by activating the caspase cascade more effectively than the same concentrations of free OSU03012. The iRGD-nanocages show great potential as a novel nanocarrier for pancreatic cancer-targeted drug delivery.
authors: Masaharu
authors: M
authors: Murata
authors: Sayoko
authors: S
authors: Narahara
authors: Takahito
authors: T
authors: Kawano
authors: Nobuhito
authors: N
authors: Hamano
authors: Jing Shu
authors: JS
authors: Piao
authors: §Department of Biomedical Engineering, National Cerebral and Cardiovascular Center Research Institute, Osaka 565-8565, Japan.
authors: Jeong-Hun
authors: JH
authors: Kang
authors: Kenoki
authors: K
authors: Ohuchida
authors: ⊥Laboratory of Tumor Biology, Takasaki University of Health and Welfare, Takasaki, Gunma 370-0033, Japan.
authors: Takashi
authors: T
authors: Murakami
authors: Makoto
authors: M
authors: Hashizume
mesh_terms: D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008856:Microscopy, Fluorescence; D049329:Nanostructures / Q000737:chemistry*; D039942:Neuropilin-1 / Q000737:chemistry*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D039942:Neuropilin-1
keywords: drug delivery system; neuropilin-1; pancreatic cancer; protein nanocages