| Previously, the successful delivery of RNase A modified with a reactive oxygen species (ROS) responsive modification (RNase A-NBC) to tumor cells, showed cancer specific induced cytotoxicity. Here, we propose a novel combination formulation comprised of Glucose Oxidase (GOx), a ROS-generating protein, and RNase A-NBC delivered using lipidoid nanoparticles. The feasibility and optimization of this combination formulation was first evaluated based on the toxicity of each protein independently delivered to HeLa tumor cells. Subsequently, the lipidoid co-delivery of proteins was evaluated and optimized. In addition, the combination formulation demonstrated a synergistic drug effect as it induced a higher death rate of HeLa cells than the arithmetic sum of GOx or RNase A-NBC alone. Finally, the glucose dependence of the cytotoxicity was also demonstrated by GLUT inhibition experiments. These results suggest a strong potential for this GOx & RNase A-NBC combination formulation to be applied in future cancer treatment. |
