Potential mitochondrial ROS-mediated damage induced by chitosan nanoparticles bee venom-loaded on cancer cell lines

Recently, numerous studies have confirmed the importance of chitosan nanoparticles (CNP) as a viable drug delivery carrier for increasing the efficacy of anticancer drugs in cancer treatment. It is a macromolecule and natural biopolymer compound, more stable and safer in use than metal nanoparticles. Bee venom (BV), a form of defense venom, has been shown to have anti-tumor, neuroprotective, anti-inflammatory, analgesic, and anti-infectivity properties. Moreover, the regulation of cell death has been linked to reactive oxygen species (ROS)-mediated cell apoptosis, which induces mitochondrial damage and ER stress through oxidative stress events. Therefore, this study aimed to illustrate the ROS-mediated effect on the cancer cells treatment with CNP-loaded BV (CNP-BV) and explained the adverse effects of ROS generation on Mitochondria and ER. We have found that the targeted CNP-BV were high in cytotoxicity against MCF-7 (IC₅₀ 437.2 μg/mL) and HepG2 (IC₅₀ 109.5 μg/mL) through the induction of massive generation of ROS, which in turn results in activating the mitochondrial cascade and ER stress. These results highlighted the role of ROS generation in inducing apoptosis in cancer cells.