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

Abstract

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.

The study of toxicity and pathogenicity risk of Potato Virus X/Herceptin nanoparticles as agents for cancer therapy

“…SDS-PAGE and purity assessment of PVX were determined by a single protein band (27 kDa) and A260:280 ratio of 1.2, respectively. Recently, the conjugation of PVX to Herceptin (PVX-HER) was confirmed (Esfandiari et al 2016). In the present study, the pathogenicity of PVX-HER in the plants was investigated by mechanical inoculation, ELISA, Western blot, and RT-PCR.…”

“…In the present study, a filamentous virus was used due to some advantages to isometric viruses, although most plant viruses employed for drug carriers are isometric (Esfandiari et al 2016).…”

“…However, Herceptin is extremely expensive drug with a wide range of unpleasant side effects. The conjugation of Herceptin to nanoparticles can enhanced the efficacy and reduce dosage and side effects among breast cancer patients (Esfandiari et al 2016).…”

“…Based on the previous study, PVX nanoparticles, as the result of conjugation of PVX to Herceptin (PVX-HER), could significantly increase the death rate of cancer cells (Esfandiari 2013;Esfandiari et al 2016). VNPs have been studied from a different environmental perspective, which is regarded as the big concern in using viruses as nanoparticles.…”

“…In addition, PVX-HER increased the death of HER2+ breast cancer cells (SKBR3 and SKOV3) in comparison to the free Herceptin (free-HER) (Esfandiari et al 2016).…”