Design and Function of Engineered Protein Nanocages as a Drug Delivery System for Targeting Pancreatic Cancer Cells via Neuropilin-1

作者：Murata Masaharu^*; Narahara Sayoko; Kawano Takahito; Hamano Nobuhito; Piao Jing Shu; Kang Jeong Hun; Ohuchida Kenoki; Murakami Takashi; Hashizume Makoto

来源：Molecular Pharmaceutics, 2015, 12(5): 1422-1430.

DOI：10.1021/mp5007129

• drug delivery system
• protein nanocages
• pancreatic cancer
• neuropilin-1

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.

• 出版日期2015-5