Ginsenoside Rg3 Reduces the Toxicity of Graphene Oxide Used for pH-Responsive Delivery of Doxorubicin to Liver and Breast Cancer Cells

Abstract

Doxorubicin (DOX) is extensively used in chemotherapy, but it has serious side effects and is inefficient against some cancers, e.g., hepatocarcinoma. To ameliorate the delivery of DOX and reduce its side effects, we designed a pH-responsive delivery system based on graphene oxide (GO) that is capable of a targeted drug release in the acidic tumor microenvironment. GO itself disrupted glutathione biosynthesis and induced reactive oxygen species (ROS) accumulation in human cells. It induced IL17-directed JAK-STAT signaling and VEGF gene expression, leading to increased cell proliferation as an unwanted effect. To counter this, GO was conjugated with the antioxidant, ginsenoside Rg3, prior to loading with DOX. The conjugation of Rg3 to GO significantly reduced the toxicity of the GO carrier by abolishing ROS production. Furthermore, treatment of cells with GO–Rg3 did not induce IL17-directed JAK-STAT signaling and VEGF gene expression—nor cell proliferation—suggesting GO–Rg3 as a promising drug carrier. The anticancer activity of GO–Rg3–DOX conjugates was investigated against Huh7 hepatocarcinoma and MDA-MB-231 breast cancer cells. GO–Rg3–DOX conjugates significantly reduced cancer cell viability, primarily via downregulation of transcription regulatory genes and upregulation of apoptosis genes. GO–Rg3 is an effective, biocompatible, and pH responsive DOX carrier with potential to improve chemotherapy—at least against liver and breast cancers.

Effects of Film Confinement on Dielectric and Electrical Properties of Graphene Oxide and Reduced Graphene Oxide-Based Polymer Nanocomposites: Implications for Energy Storage

“…Figure S9d shows that the rGO sheet is around 3 nm, which indicates the sheet is three layered. The literature also showed the presence of layers in other nanofiller-based studies as well. − However, due to sonication, rGO has less number of layers in one sheet compared to GO. The bright white areas in the GO/rGO AFM images suggest sheet folding or layers .…”

Cytotoxicity of Carbon Nanotubes, Graphene, Fullerenes, and Dots

“…Figure 7c shows Rg3, DOX, and graphene oxide cytotoxicity in human breast cancer MDA-MB-231 cells [27]. AlamarBlue assay 24 h after GO, GO-Rg3, GO-Rg3-DOX treatment is shown together with ROS production.…”

“…Authors of Ref. [27] performed the studies of cytotoxicity of graphene oxide and GO-Ginsenoside (Rg3)-Doxorubicin against Huh7 cells. Figure 7(b1) shows the transmission electron microscopy images of treated cells.…”

“…Figure 7(b4) shows reactive oxygen species (ROS). Figure 7(b5) shows schematics of GO-Rg3-DOX internalization [27].…”

“…The toxicology of carbon nanomaterials was studied for carbon nanotubes [1][2][3][4][5][6][7][8][9][10][11][12][13][14], graphene [15][16][17][18][19][20][21][22][23][24][25][26][27][28], fullerenes [29][30][31][32][33], and dots [34][35][36][37][38]. Most of the work deals with microorganisms, animals, and humans.…”