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.
Department of Micro and Nanotechnology, Technical University of Denmark, Ørsteds Plads, 2800 Kgs, Lyngby, Denmark. neda.esfandiari@yahoo.com.|Department of Plant Protection, Faculty of Sciences and Plant Protection, Tehran University, Tehran, Iran. neda.esfandiari@yahoo.com.
Neda
N
Esfandiari
Division of Hematology, Department of Medicine, Karolinska Institute, Karolinska University Hospital, SE14186, Stockholm, Sweden.
Mohsen Karimi
MK
Arzanani
Department of Hematology, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran.
Masoud
M
Soleimani
Department of Plant Protection, Faculty of Sciences and Plant Protection, Tehran University, Tehran, Iran.
Mina
M
Kohi-Habibi
Department of Micro and Nanotechnology, Technical University of Denmark, Ørsteds Plads, 2800 Kgs, Lyngby, Denmark.
Winnie E
WE
Svendsen
D000970:Antineoplastic Agents / Q000737:chemistry; D017209:Apoptosis; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D017863:Potexvirus; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology; D014026:Nicotiana / Q000821:virology; D000068878:Trastuzumab / Q000737:chemistry*
D000970:Antineoplastic Agents; D004337:Drug Carriers; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
Cancer; HER2+ cell lines; Immunological test; Plant viral nanoparticles