Graphene Oxide Modified Microbubble for the Ultrasonic Imaging and Treatment of Hepatocellular Carcinoma

Abstract

The ultrasound microbubbles modified with the nanomaterial GO not only allow real-time monitoring of liver blood flow for disease diagnosis but also serve as drug delivery carriers, offering the dual benefits of diagnostic imaging and targeted therapy. This presents a highly promising strategy for the integrated diagnosis and treatment of hepatocellular carcinoma (HCC) patients. In this study, L-theanine (TH), a natural polyphenol with antioxidant, and antitumor, was used as a “green” reducing agent for graphene oxide (GO) to prepare nanoscale reduced graphene oxide (rGO-TH), which was then blended with SonoVue microbubbles to prepare composite microbubbles (SV@rGO-TH MBs) for the integrated diagnosis and treatment of HCC. The SV@rGO-TH MBs remain stable at higher Mechanical Index (MI), thereby enhancing contrast-enhanced ultrasound(CEUS) imaging effects and improving the accuracy of disease diagnosis. SV@rGO-TH MBs show significant antitumor activity, inhibiting HepG2 cancer cell growth in vivo and in vitro. Furthermore, combined with ultrasound irradiation, nanoscale rGO-TH more easily penetrates the vascular walls and accumulates in tumor tissues, enhancing the antitumor effect. Our research demonstrates that SV@rGO-TH MBs are a safe and effective ultrasound contrast agent (UCA) for the integrated diagnosis and treatment of HCC, providing insights for the early diagnosis and precise treatment of tumors.