Vitis vinifera Kyoho-derived exosome-like nanoparticles-based drug delivery and therapeutic modalities for breast cancer therapy

Fruit-derived exosomes have the capability to deliver drugs and target disease cells. In this primary, Vitis vinifera Kyoho-isolated exosome-like nanoparticles (VKENPs) were extracted and delivered with and without multiple drugs to investigate therapeutic modalities for drug delivery and in vitro breast tumor (BT) treatment. For this purpose, VKENPs were isolated through simple single-step centrifugation and 0.22 mu m pore size filtration method and ultra-centrifugation at 100,000xg. Multiple drugs such as metformin, doxorubicin, and tamoxifen were loaded and delivered to the BT cells to assess cellular internalization time, viability, cytotoxicity, ROS generation, and apoptosis. The isolated VKENP's average size was 40 nm with a good polydispersity (113.1 +/- 0.117 PDI Mw) and zeta potential (-23 mV), negligibly cytotoxic to healthy tissues (10 % cytotoxicity) along with rapid cellular internalization (within 6 h), and are biased towards tumors by killing 56 % 4T1 cells at 72 h. Moreover, VKEMDT induced 90 % cell death in BT cells via enhancing ROS generation level and inducing apoptosis and necrosis cell death channels. Therefore, the prepared VKENPs successfully induced cell death and have the potential to load multiple drugs with effective targeting of tumor cells. Thus, VKENPs may expand the scope of drug therapies while reducing the off-target effects.