Engineered protein nanoparticles for in vivo tumor detection

Abstract

Two different protein nanoparticles that are totally different in shape and surface structure, i.e. Escherichia coli DNA-binding protein (eDPS) (spherical, 10 nm) and Thermoplasma acidophilum proteasome (tPTS) (cylindrical, 12 x 15 nm) were engineered for in vivo 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 (alpha(v)beta(3)) 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 in vivo 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 in vivo tumor detection. (C) 2014 Elsevier Ltd. All rights reserved.