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

doxorubicin

drug carrier

graphene oxide

Author

Shadi Rahimi

Chalmers, Life Sciences, Systems and Synthetic Biology

Daniel van Leeuwen

Chalmers, Life Sciences, Chemical Biology

Fariba Roshanzamir

Chalmers, Life Sciences, Systems and Synthetic Biology

Santosh Pandit

Chalmers, Life Sciences, Systems and Synthetic Biology

Lei Shi

Chalmers, Life Sciences, Systems and Synthetic Biology

Nima Sasanian

Chalmers, Life Sciences, Chemical Biology

Jens B Nielsen

Chalmers, Life Sciences, Systems and Synthetic Biology

BioInnovation Institute

Elin Esbjörner Winters

Chalmers, Life Sciences, Chemical Biology

Ivan Mijakovic

Chalmers, Life Sciences, Systems and Synthetic Biology

Technical University of Denmark (DTU)

Pharmaceutics

19994923 (eISSN)

Vol. 15 2 391

Graphene-based CRISPR-Cas 9 gene modification to plant cells

Novo Nordisk Foundation (NNF20OC0064547), 2021-04-01 -- 2023-12-31.

Funktionell leverans av nukleotid-baserade läkemedel

Swedish Foundation for Strategic Research (SSF) (IRC15-0065), 2017-03-01 -- 2024-12-31.

Development of graphene-based antibacterial surface for medical devices - Effective, safe and affordable

VINNOVA (2020-00792), 2020-06-01 -- 2022-05-31.

Subject Categories

Cell Biology

Cell and Molecular Biology

Cancer and Oncology

DOI

10.3390/pharmaceutics15020391

PubMed

36839713

More information

Latest update

3/13/2023