Cavitation-Enhanced Delivery of the Nanomaterial Graphene Oxide-Doxorubicin to Hepatic Tumors in Nude Mice Using 20 kHz Low-Frequency Ultrasound and Microbubbles

Abstract

Graphene oxide (GO) is a kind of nanomaterial. Here, we explored its application in tumor treatment. We loaded doxorubicin onto the surface of GO to form graphene oxide-doxorubicin (GO-DOX). After injection of the contrast agent SonoVue microbubbles (MBs) into the tail vein of tumor-bearing nude mice, subcutaneous hepatic carcinomas inoculated with the HepG2 cell line were irradiated with 20 kHz low-frequency ultrasound (US). Subsequently, GO-DOX was injected into the tail vein of nude mice. Transmission electron microscopy (TEM) and TUNEL assays were performed to observe the curative effects. Biocompatibility tests of GO-DOX included routine blood cell counts, blood smears, serum biochemical assays, and histological sampling of important organs. It was found that the nanomaterial GO-DOX promoted apoptosis of tumor cells in nude mice. TEM of the USMB+GO-DOX treatment showed vascular endothelial cell wall rupture, widened endothelial cell gaps, black granules in the vascular lumen, interstitial erythrocyte leakage, and apparent apoptosis of tumor cells. There were no toxic side effects of GO-DOX on the blood system and in the major organs of these mice. Ultrasound cavitation destroys tumor blood vessels and enhances the release of nanomaterials to tumor cells of nude mice.