Engineered protein nanoparticles for invivo tumor detection

Keum Young Ahn, Ho Kyung Ko, Bo Ram Lee, Eun Jung Lee, Jong Hwan Lee, Youngro Byun, Ick Chan Kwon, Kwangmeyung Kim, Jeewon Lee

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Two different protein nanoparticles that are totally different in shape and surface structure, i.e. Escherichia coli DNA-binding protein (eDPS) (spherical, 10nm) and Thermoplasma acidophilum proteasome (tPTS) (cylindrical, 12×15nm) were engineered for invivo optical tumor detection: arginine-glycine-aspartic acid (RGD) peptide (CDCRGDCFC) was genetically inserted to the surface of each protein nanoparticle, and also near-infrared fluorescence dye was chemically linked to the surface lysine residues. The specific affinity of RGD for integrin (αvβ3) facilitated the uptake of RGD-presenting protein nanoparticles by integrin-expressing tumor cells, and also the protein nanoparticles neither adversely affected cell viability nor induced cell damage. After intravenously injected to tumor-bearing mice, all the protein nanoparticles successfully reached tumor with negligible renal clearance, and then the surface RGD peptides caused more prolonged retention of protein nanoparticles in tumor and accordingly higher fluorescence intensity of tumor image. In particular, the fluorescence of tumor image was more intensive with tPTS than eDPS, which is due presumably to longer invivo half-life and circulation of tPTS that originates from thermophilic and acidophilic bacterium. Although eDPS and tPTS were used as proof-of-concept in this study, it seems that other protein nanoparticles with different size, shape, and surface structure can be applied to effective invivo tumor detection.

Original languageEnglish
Pages (from-to)6422-6429
Number of pages8
JournalBiomaterials
Volume35
Issue number24
DOIs
StatePublished - Aug 2014

Bibliographical note

Funding Information:
This study was supported by the 2012 NLRL (National Leading Research Lab.) Project (grant no. 2012R1A2A1A01008085 ) (the main project that supported this work) and the Basic Science Research Program (ERC program, grant no. 2010-0029409 ) of the National Research Foundation of Korea (NRF) .

Keywords

  • Optical imaging
  • Protein nanoparticles
  • Surface engineering
  • Tumor detection

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