Design of Bio-Graphene-Based Multifunctional Nanocomposites Exhibits Intracellular Drug Delivery in Cervical Cancer Treatment

Abstract

The advent of bio-nanotechnology has revolutionized nanodrug delivery by improving drug efficacy and safety. Nevertheless, acceptable carriers for therapeutic molecules are one of the most difficult challenges in drug delivery. Graphene material-based (GMB) and polymer-based drug-loaded nanocarriers have both demonstrated clinical advantages in delivering drugs of interest in vitro/in vivo. Cisplatin (CDDP) is an inorganic chemotherapeutic drug that is commonly used to treat a variety of cancers. However, its clinical use is associated with drug resistance and few side effects, which reduces its antitumor effects. Therefore, we developed a CDDP-loaded chitosan-functionalized graphene oxide nanocomposite (CDDP@CS-GO NC)-based nanodrug delivery system (NDDS). Flow cytometry and confocal imaging show that the CDDP@CS-GO NCs lead to significantly increased intracellular drug accumulation in tumor cells. Cancer cells take up the nanocomposite via endocytosis and can generate intracellular reactive oxygen species (ROS) to increase mitochondrial membrane potential loss (Δψm) and enable cytochrome-c release, followed by the dysregulation of Bcl-2 into the cytosol and activation of caspase-3 to induce cancer cell apoptosis. In vitro experiments demonstrated the excellent cancer therapeutic effect with few side effects of the carriers. CDDP@CS-GO NCs are expected to play an important role in responsive NDDSs for cancer therapy.