Design and function of engineered protein nanocages as a drug delivery system for targeting pancreatic cancer cells via neuropilin-1

Masaharu Murata, Sayoko Narahara, Takahito Kawano, Nobuhito Hamano, Jing Shu Piao, Jeong Hun Kang, Kenoki Ohuchida, Takashi Murakami, Makoto Hashizume

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1422-1430
Number of pages9
JournalMolecular pharmaceutics
Volume12
Issue number5
DOIs
Publication statusPublished - May 4 2015

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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