Folic acid functionalization of rGO/Co₃O₄/chitosan based biocompatible nanocomposite enhances targeted delivery and cytotoxicity of doxorubicin

Metal-based nanocomposites address various challenges in chemotherapy such as biocompatibility, bioavailability, and targeted therapy. Cobalt containing nanocomposites can support multimodal therapy with its inherent catalytic ability to generate ROS, enhanced drug loading, pH responsive drug release, improved biocompatibility, and chemical stability apart from its paramagnetic property. Here, we report fabrication and characterization of nanocomposite (GCC) composed of cobalt oxide nanoparticles (Co₃O₄) incorporated with reduced graphene oxide (rGO) and chitosan (Cs) as substrates and functionalized with folic acid (FA) for targeted delivery and enhanced anti-cancer activity of doxorubicin (Dox) incorporated on GCC. Site-targeted delivery and apoptosis mediated cell death was observed where GCC functionalized with Dox & FA (GCC/Dox-FA) showed significantly higher cytotoxicity on A549 and MCF-7 cells compared to GCC/Dox. Site targeted delivery of GCC/Dox was achieved with folic acid, while cytotoxicity was rendered by Dox and partly by GCC with its inherent ROS generating ability. Significant drug loading and pH dependent drug release was executed by the substrates (rGO & Cs) and Co₃O₄, respectively. GCC demonstrated highest loading of 0.428 mg of Dox/mg of nanocomposite and at 0.4 mg/mL of Dox, the highest loading percentage was achieved (95.25 %). Biocompatibility of GCC was established in zebrafish which showed that the nanocomposite neither induced any significant abnormalities nor affected the survival rate after the microinjection. Overall, this work reports the successful combination of classical chemotherapy with Doxorubin and advanced biocompatible nano drug delivery system (GCC) for improved therapeutic management of cancer.