Targeting Breast Cancer With Bio-inspired Virus Nanoparticles

Background: Viral nanoparticles are biodegradable, biocompatible, selfassembling, and highly symmetric, and can be produced in large quantities. Several plant viral nanoparticles (VNPs) have been exploited in different areas of nanobiotechnology, especially drug delivery in cancer therapy. In this study, a flexuous plant virus called potato virus X (PVX) is presented with a unique nanoarchitecture which can increase tumor homing and penetration. Thus, this study aimed to investigate the potential of PVX for delivering Herceptin (HER) in different breast cancer cells and normal cells. Methods: PVX was conjugated to HER by EDC/Sulfo-NHS in two steps. After confirming the conjugation, PVX-HER efficacy and drug activity were investigated in HER2-positive (SKBR3 and SKOV3), HER2-negative (MCF-7 and MDA-MBA-21), and non-tumorigenic epithelia breast cancer (MCF-12A) cell lines after treatment with 10 and 20 μg of the drug. Then, PVX-HER was imaged in SKBR3 cells in to study the nuclear accumulation of the drug at different concentrations. Results: An increased cytotoxic efficiency was observed for PVX-HER vs free-HER in SKBR3 and SKOV3 cell lines. However, the efficacy of PVX-HER failed to increase in MCF-7, MDA-MB-231, and MCF-12A cell lines compared with free-HER after 24 hours. In addition, compared with free-HER, Herceptin nuclear accumulation was increased in SKBR3 cells treated with PVX-HER. Further, the PVX-HER treatment resulted in reduced tumor growth in the HER2- positive cells lines. Finally, a direct relationship was observed between the imaging results and MTT assay in SKBR3. Conclusion: PVX-HER displays a significantly greater cytotoxic activity compared with free-HER in HER2-positive cells.