Graphene-Based Nanocomposites against Hepatocellular Carcinoma via Chemo/Photothermal/Photodynamic Synergistic Therapy

Single chemotherapy (CT) has difficulty meeting the clinical needs of patients with intermediate and advanced hepatocellular carcinoma (HCC). To solve this problem, graphene-based nanocomposites (DOX/IR820@GNPs) were prepared and used to combat HCC through combined photothermal therapy (PTT), photodynamic therapy (PDT), and CT by using membrane-penetrating peptide (tLyp-1) and hyaluronic acid as tumor-targeting materials and IR820@GQDs and doxorubicin hydrochloride (DOX) as photosensitizer and chemotherapeutic drug. The nanocomposites were well dispersed in water with the particle size of 98–145 nm and zeta of −6.0 ∼ −12.8 mV and have absorption in the UV, visible, and near-infrared (NIR) regions. Therefore, DOX/IR820@GNPs not only have the capability of fluorescence imaging but also produce reactive oxygen species and photothermal effects under NIR irradiation. In addition, the nanocomposites are biocompatible, can be internalized into HepG2 cells and enriched at the tumor site by dual targeting, and can accelerate the release of DOX in the tumor microacid environment. Importantly, due to the above properties, DOX/IR820@GNPs can be used in PTT and PDT to kill tumors directly under NIR irradiation. Meanwhile, the CT effect of DOX is enhanced in tumor microacid and high-temperature environments. Finally, the optimal anti-HCC effect was achieved by the synergistic sensitization of PTT/PDT and CT.