Ginsenoside Rg3 Reduces the Toxicity of Graphene Oxide Used for pH-Responsive Delivery of Doxorubicin to Liver and Breast Cancer Cells
Artikel i vetenskaplig tidskrift, 2023

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.

ginsenoside Rg3

drug delivery


drug carrier

graphene oxide


Shadi Rahimi

Chalmers, Life sciences, Systembiologi

Daniel van Leeuwen

Chalmers, Life sciences, Kemisk biologi

Fariba Roshanzamir

Chalmers, Life sciences, Systembiologi

Santosh Pandit

Chalmers, Life sciences, Systembiologi

Lei Shi

Chalmers, Life sciences, Systembiologi

Nima Sasanian

Chalmers, Life sciences, Kemisk biologi

Jens B Nielsen

Chalmers, Life sciences, Systembiologi

BioInnovation Institute

Elin Esbjörner Winters

Chalmers, Life sciences, Kemisk biologi

Ivan Mijakovic

Chalmers, Life sciences, Systembiologi

Danmarks Tekniske Universitet (DTU)


19994923 (eISSN)

Vol. 15 2 391

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