Triple-enzyme mimetic hemocompatible nanoparticles for glioblastoma targetingviapH-responsive enhanced ROS generation

Oxidative stress is characteristic of glioblastoma and other cancers, often facilitating tumor proliferation and resistance to treatment. Herein, a biocompatible synthesis approach for gold (Au), silver (Ag), and three different bimetallic (Au-Ag) nanoparticles using ayurvedic formulation of Bauhinia variegata (Kachnar) is developed to target glioblastoma via pH-responsive enhanced reactive oxygen species (ROS) generation. By employing the reducing and stabilizing capabilities of plant-derived ayurvedic formulation, Au, Ag and Au-Ag nanoparticles are engineered with regulated surface chemistry. These nanoparticles demonstrated pH-dependent multi-enzyme mimetics (catalase-, peroxidase- and superoxide dismutase-like), hemocompatibility towards red blood cells (RBCs), and blood-brain barrier (BBB) penetrability. Experiments on human glioblastoma (LN229), human peripheral blood mononuclear cells (hPBMCs) and human embryonic kidney (HEK293) cells established that the synthesized nanozymes show a ROS-mediated effect inside glioblastoma cells, while concurrently attenuating intracellular oxidative stress in non-malignant cells. Interestingly, the pH dependent enzymatic assays confirmed elevated peroxidase-like activity at acidic pH in context to tumour microenvironment (TME), whereas improved catalase-like activity at neutral pH refers to healthy cell conditions. Overall, the study offers potential use of multi-enzyme mimetic ayurvedic drug loaded nanoparticles for targeted glioblastoma action and possible biomedical utility.