TY - JOUR
T1 - Lipid-Functionalized Graphene Loaded with hMnSOD for Selective Inhibition of Cancer Cells
AU - Farell, Megan
AU - Self, Ava
AU - Guza, Christine
AU - Song, Hyewon
AU - Apollon, Luigi
AU - Gomez, Esther W.
AU - Kumar, Manish
N1 - Funding Information:
This material is based on the work supported by the National Science Foundation Graduate Research Fellowship Program under Grant No. DGE1255832 and in part by NSF CBET-1552571 and NSF EEC-1659497. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation. The authors would like to acknowledge Dr. Andrew Zydney for the use of his microplate reader in this study.
Publisher Copyright:
Copyright © 2020 American Chemical Society.
PY - 2020/3/18
Y1 - 2020/3/18
N2 - Combination therapies utilize multiple mechanisms to target cancer cells to minimize cancer cell survival. Graphene provides an ideal platform for combination therapy due to its photothermal properties and high loading capacity for cancer-fighting molecules. Lipid functionalization of graphene extends its potential as a therapeutic platform by improving its biocompatibility and functionality. Previous studies involving graphene demonstrated its usage as a therapeutic vehicle; however, the effect of bare and engineered graphene structures on oxidative stress has not been comprehensively investigated. Because oxidative stress has been linked to cancer progression, it is vital to examine the generation of reactive oxygen species (ROS) in response to therapeutic platforms. This study functionalizes reduced graphene oxide (rGO) with lipids and the antioxidant enzyme human manganese superoxide dismutase (hMnSOD) and presents a detailed characterization of cellular responses to bare and functionalized rGO nanostructures in tumorigenic and nontumorigenic breast cell lines. Each cell type displayed distinct responses depending on whether they were normal, nonmetastatic, or metastatic cells. Bare rGO significantly reduced cell growth and substantially increased ROS production in all cell lines and instigated necrosis in metastatic breast cancer cells. Cell proliferation decreased in cancerous breast cells upon introduction of lipid-rGO, which correlated with peroxidation of lipids coating the rGO. In contrast, lipid-rGO nanostructures had minimal impact on proliferation and lipid peroxidation for normal breast cells. Lipid-rGO nanostructures with bound hMnSOD inhibited the proliferation of metastatic cancer cells while preventing necrosis and avoiding the negative side effects on normal cells associated with chemotherapeutic agents. Together, the results confirm the importance of functionalizing rGO for therapeutic applications and present an additional modality for the usage of graphene to selectively target cancer cells.
AB - Combination therapies utilize multiple mechanisms to target cancer cells to minimize cancer cell survival. Graphene provides an ideal platform for combination therapy due to its photothermal properties and high loading capacity for cancer-fighting molecules. Lipid functionalization of graphene extends its potential as a therapeutic platform by improving its biocompatibility and functionality. Previous studies involving graphene demonstrated its usage as a therapeutic vehicle; however, the effect of bare and engineered graphene structures on oxidative stress has not been comprehensively investigated. Because oxidative stress has been linked to cancer progression, it is vital to examine the generation of reactive oxygen species (ROS) in response to therapeutic platforms. This study functionalizes reduced graphene oxide (rGO) with lipids and the antioxidant enzyme human manganese superoxide dismutase (hMnSOD) and presents a detailed characterization of cellular responses to bare and functionalized rGO nanostructures in tumorigenic and nontumorigenic breast cell lines. Each cell type displayed distinct responses depending on whether they were normal, nonmetastatic, or metastatic cells. Bare rGO significantly reduced cell growth and substantially increased ROS production in all cell lines and instigated necrosis in metastatic breast cancer cells. Cell proliferation decreased in cancerous breast cells upon introduction of lipid-rGO, which correlated with peroxidation of lipids coating the rGO. In contrast, lipid-rGO nanostructures had minimal impact on proliferation and lipid peroxidation for normal breast cells. Lipid-rGO nanostructures with bound hMnSOD inhibited the proliferation of metastatic cancer cells while preventing necrosis and avoiding the negative side effects on normal cells associated with chemotherapeutic agents. Together, the results confirm the importance of functionalizing rGO for therapeutic applications and present an additional modality for the usage of graphene to selectively target cancer cells.
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U2 - 10.1021/acsami.9b20070
DO - 10.1021/acsami.9b20070
M3 - Article
C2 - 32077682
AN - SCOPUS:85082095697
VL - 12
SP - 12407
EP - 12416
JO - ACS applied materials & interfaces
JF - ACS applied materials & interfaces
SN - 1944-8244
IS - 11
ER -