A new application of plant virus nanoparticles as drug delivery in breast cancer

Nanoparticles based on non-pathogenic viruses have opened up a novel sector in nanotechnology. Viral nanoparticles based on plant viruses have clear advantages over any synthetic nanoparticles as they are biocompatible and biodegradable self-assembled and can be produced inexpensively on a large scale. From several such under-development platforms, only a few have been characterized in the target-specific drugs into the cells. Potato virus X is presented as a carrier of the chemotherapeutic drug Herceptin that is currently used as a targeted therapy in (HER2+) breast cancer patients. Here, we used nanoparticles formed from the potato virus X to conjugate the Herceptin (Trastuzumab) monoclonal antibody as a new option in specific targeting of breast cancer. Bioconjugation was performed by EDC/sulfo-n-hydroxysuccinimide (sulfo-NHS) in a two-step protocol. Then, the efficiency of conjugation was investigated by different methods, including sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), Western blot, ELISA, Zetasizer, and transmission electron microscopy. SDS-PAGE and Western blot analysis confirmed an 82-kDa protein band that resulted from conjugation of potato virus X (PVX) coat protein (27 kDa) to heavy chain of Herceptin (55 kDa). Zeta potential values for conjugated particles, PVX, and HER were −7.05, −21.4, and −1.48, respectively. We investigated the efficiency of PVX-Herceptin to induce SK-OV-3 and SK-BR-3 cells (HER2 positive cell lines) apoptosis. We therefore counted cells and measured apoptosis by flow cytometry assay, then compared with Herceptin alone. Based on our data, we confirmed the conjugation of PVX and Herceptin. This study suggests that the PVX-Herceptin conjugates enable Herceptin to become more potential therapeutic tools.

[1]  M. Young,et al.  2-D array formation of genetically engineered viral cages on au surfaces and imaging by atomic force microscopy. , 2003, Journal of the American Chemical Society.

[2]  Thommey P. Thomas,et al.  Nanoparticle targeting of anticancer drug improves therapeutic response in animal model of human epithelial cancer. , 2005, Cancer research.

[3]  Andries Zijlstra,et al.  Viral nanoparticles as tools for intravital vascular imaging , 2006, Nature Medicine.

[4]  Thommey P. Thomas,et al.  HER2 specific tumor targeting with dendrimer conjugated anti-HER2 mAb. , 2006, Bioconjugate chemistry.

[5]  Trevor Douglas,et al.  Viruses: Making Friends with Old Foes , 2006, Science.

[6]  Duane E. Prasuhn,et al.  Bio-distribution, toxicity and pathology of cowpea mosaic virus nanoparticles in vivo. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[7]  Joo‐Hang Kim,et al.  Retargeting of adenoviral gene delivery via Herceptin-PEG-adenovirus conjugates to breast cancer cells. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[8]  A. Karlström,et al.  (99m)Tc-maEEE-Z(HER2:342), an Affibody molecule-based tracer for the detection of HER2 expression in malignant tumors. , 2007, Bioconjugate chemistry.

[9]  C. Hudis Trastuzumab--mechanism of action and use in clinical practice. , 2007, The New England journal of medicine.

[10]  C. Lico,et al.  Viral vectors for production of recombinant proteins in plants , 2008, Journal of cellular physiology.

[11]  G. Liu,et al.  Targeted Herceptin–dextran iron oxide nanoparticles for noninvasive imaging of HER2/neu receptors using MRI , 2009, JBIC Journal of Biological Inorganic Chemistry.

[12]  Warren C W Chan,et al.  Mediating tumor targeting efficiency of nanoparticles through design. , 2009, Nano letters.

[13]  Gary Siuzdak,et al.  Endothelial Targeting of Cowpea Mosaic Virus (CPMV) via Surface Vimentin , 2009, PLoS pathogens.

[14]  T. Hohn,et al.  Complete genome sequence of an Iranian isolate of Potato virus X from the legume plant Pisum sativum , 2009, Virus Genes.

[15]  John E. Johnson,et al.  Potato virus X as a novel platform for potential biomedical applications. , 2010, Nano letters.

[16]  L. Santi,et al.  Viral nanoparticles as macromolecular devices for new therapeutic and pharmaceutical approaches. , 2010, International journal of physiology, pathophysiology and pharmacology.

[17]  N. Steinmetz Viral nanoparticles as platforms for next-generation therapeutics and imaging devices. , 2010, Nanomedicine : nanotechnology, biology, and medicine.

[18]  Akin Aliosmanoglu,et al.  Nanotechnology in Cancer Treatment , 2012 .

[19]  J. E. Mealy,et al.  Interior engineering of a viral nanoparticle and its tumor homing properties. , 2012, Biomacromolecules.

[20]  Alaa A. A. Aljabali,et al.  CPMV-DOX delivers. , 2013, Molecular pharmaceutics.

[21]  A. Jemal,et al.  Cancer statistics, 2014 , 2014, CA: a cancer journal for clinicians.

[22]  A. Armuss [Breast cancer update]. , 2014, Versicherungsmedizin.