Targeted cowpea chlorotic mottle virus-based nanoparticles with tumor-homing peptide F3 for photothermal therapy
- 49 Downloads
Our aim was to devise targeted drug delivery systems using genetically modified cowpea chlorotic mottle virus (CCMV) capsids by fusion expression with tumorhoming peptide F3 for efficient delivery of therapeutic substances into tumor cells. The RNA-binding domain at the N terminus (amino acid residues 1–25) of CCMV capsid protein (CP) was selectively deleted, and F3 was inserted for the expression in Pichia pastoris. After chromatographic purification, F3-CCMV capsids were obtained via selfassembly of the F3-CP fusion protein and then analyzed by transmission electron microscopy and dynamic light scattering analysis, which revealed spherical nanoparticles (NPs) ca. 18 nm in diameter with regular monodispersity. Near-infrared fluorescent dye IR780 iodide, which has been applied for cancer imaging, photodynamic therapy, and photothermal therapy, was encapsulated in F3-CCMV NPs. The resultant F3-CCMV-IR780 NPs showed excellent molecular targeting to nucleolin receptor overexpressed on the surface of MCF-7 tumor cells. Furthermore, the in vitro cellular uptake and cell viability assay proved a photothermal effect by a single dose of near-infrared laser irradiation. The present system may offer a programmable nanoscaffoldbased drug delivery system vehicle for fabrication of promising therapeutic substances for cancer therapy.
KeywordsCCMV NIR dye tumor-homing drug delivery photothermal therapy
Unable to display preview. Download preview PDF.
- 7.Strable, E. and M. G. Finn (2009) Chemical modification of viruses and virus-like particles. Curr. Top. Microbiol. Immunol. 327: 1–21.Google Scholar
- 20.Kaiser, C. R., M. L. Flenniken, E. Gillitzer, A. L. Harmsen, A. G. Harmsen, M. A. Jutila, T. Douglas, and M. J. Young (2007) Biodistribution studies of protein cage nanoparticles demonstrate broad tissue distribution and rapid clearance in vivo. Int. J. Nanomed. 2: 715.Google Scholar
- 28.Reddy, G. R., M. S. Bhojani, P. McConville, J. Moody, B. A. Moffat, D. E. Hall, G. Kim, Y. L. Koo, M. J. Woolliscroft, J. V. Sugai, T. D. Johnson, M. A. Philbert, R. Kopelman, A. Rehemtulla, and B. D. Ross (2006) Vascular targeted nanoparticles for imaging and treatment of brain tumors. Clin. Cancer Res. 12: 6677–6686.CrossRefGoogle Scholar
- 30.Wu, Y., H. Yang, and H. J. Shin (2011) Expression and selfassembly of cowpea chlorotic mottle virus capsid proteins in Pichia pastoris and encapsulation of fluorescent myoglobin. Mater. Res. Soc. Symp. Proc. Doi: 10.1557/opl.2011.138.Google Scholar
- 32.Wu, Y., H. Yang, Y. J. Jeon, M. Y. Lee, J. Li, and H. J. Shin (2014) Surface modification of cowpea chlorotic mottle virus capsids via a copper (I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction and their adhesion behavior with HeLa cells. Biotechnol. Bioproc. Eng. 19: 747–753.CrossRefGoogle Scholar
- 36.Brumfield, S., D. Willits, L. Tang, J. E. Johnson, T. Douglas, and M. Young (2004) Heterologous expression of the modified coat protein of cowpea chlorotic mottle bromovirus results in the assembly of protein cages with altered architectures and function. J. Gen. Virol. 85: 1049–1053.CrossRefGoogle Scholar