Cellular and subcellular interactions of graphene-based materials with cancerous and non-cancerous cells

Rahimi, Shadi; Chen, Yanyan; Zareian, Mohsen; Pandit, Santosh; Mijaković, Ivan

doi:10.1016/j.addr.2022.114467

Cited by 32 publications

(24 citation statements)

References 146 publications

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“…Previous studies reported the influence of pristine graphene and GO on signaling pathways and their role in inducing changes in the expression and regulation of genes and proteins in various mammalian cells. − For this reason, following the exposure of bEnd.3 cells to either FLG or GO, we explored the cell proteome by obtaining label-free high-resolution LC-MS data on the cell lysates.…”

Section: Graphene Interactions With a 2d Murine Model Of Bbbmentioning

confidence: 99%

Interactions of Graphene Oxide and Few-Layer Graphene with the Blood–Brain Barrier

et al. 2023

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Thanks to their biocompatibility and high cargo capability, graphene-based materials (GRMs) might represent an ideal brain delivery system. The capability of GRMs to reach the brain has mainly been investigated in vivo and has highlighted some controversy. Herein, we employed two in vitro BBB models of increasing complexity to investigate the bionano interactions with graphene oxide (GO) and few-layer graphene (FLG): a 2D murine Transwell model, followed by a 3D human multicellular assembloid, to mimic the complexity of the in vivo architecture and intercellular crosstalk. We developed specific methodologies to assess the translocation of GO and FLG in a label-free fashion and a platform applicable to any nanomaterial. Overall, our results show good biocompatibility of the two GRMs, which did not impact the integrity and functionality of the barrier. Sufficiently dispersed subpopulations of GO and FLG were actively uptaken by endothelial cells; however, the translocation was identified as a rare event.

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Section: Graphene Interactions With a 2d Murine Model Of Bbbmentioning

confidence: 99%

Interactions of Graphene Oxide and Few-Layer Graphene with the Blood–Brain Barrier

et al. 2023

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“…rGOs and GO are extensively studied because of their capability to target irregular angiogenesis and hypoxia in the tumor microenvironment (TME). , According to previous studies, GO-doxorubicin exhibited excellent anticancer activities in breast cancer cellular models . Remarkably, the biocompatibility and biosafety of graphene and its derivatives are crucial challenging issues, which are size-, time-, and dose-dependent to various cell lines; these concerns depend on several interactions with the cell membrane and crucial components inside the cells . However, with suitable functionalization of graphene (nano)materials using safer agents, their physicochemical properties as well as biocompatibility can be significantly improved. , For instance, after the conjugation of folic acid with chitosan-modified GO nanosystems, they could be deployed for photothermal therapy of cancers with the guidance of photoacoustic imaging and near-infrared fluorescence, wherein the cancer cells were eliminated under laser irradiation (in vitro).…”

Section: Advanced Nanosystems For Targeted Cancer Therapeuticsmentioning

confidence: 99%

Advanced Nanosystems for Cancer Therapeutics: A Review

Mohajer

Mirhosseini‐Eshkevari

Ahmadi

et al. 2023

ACS Appl. Nano Mater.

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Since cancer has a very complex pathophysiology, existing cancer treatment strategies encounter several challenges such as the lack of specificity/selectivity, induction of multidrug resistance, and possible side effects/toxicity. A wide variety of organic, inorganic, and hybrid nanosystems have been designed with unique magnetic, thermal, mechanical, electrical, and optical properties for targeted cancer therapy. These advanced nanosystems with enhanced bioavailability, biocompatibility, and drug loading capacity have been developed for targeted cancer therapy to reduce toxicity and improve the targeting properties. In this context, challenges persist for their clinical translational studies and enhancement of their therapeutic efficiency as well as the optimization of synthesis conditions and large-scale production. In addition, despite promising preclinical results, the number of nanosystems available to patients is still very low, partly due to a lack of understanding of the differences among animal model species and humans that influence the behavior and functionality of these nanosystems. Regarding this, organ-on-a-chip platforms can significantly help in drug screening and delivery aspects in cancer/tumor cells as well as cancer modeling research; the organs-on-chip approach can also be helpful to analyze the cancer–immune cells interactions. Future studies should focus on the exploration of multifunctional nanosystems with synergistic chemo-photothermal, photothermal/photodynamic, and cancer immunotherapeutic potentials as well as smart nanosystems with theranostic capabilities. Herein, recent advancements pertaining to the applications of advanced nanosystems for cancer therapeutics are deliberated. Current obstacles and limitations hindering the application from research to clinical uses are also discussed while providing recommendations for a more efficient adoption of nanomaterials in the treatment of cancers.

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“…One family of efficient drug delivery systems comprises graphene-based water-soluble nanosheets. Among these, graphene oxide (GO) sheets have received considerable attention [ 7 , 8 ]. GO, an oxidized form of graphene, shows good biocompatibility and water dispersibility [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…Specifically, the protonation of amino groups on DOX leads to dissociation from GO, and the hydrogen-bonding interactions between GO and DOX are also weakened at an acidic pH [ 16 ]. However, GO itself induces the unwanted generation of intracellular ROS in a concentration and time-dependent manner [ 8 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2023

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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.

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Cellular and subcellular interactions of graphene-based materials with cancerous and non-cancerous cells

Cited by 32 publications

References 146 publications

Interactions of Graphene Oxide and Few-Layer Graphene with the Blood–Brain Barrier

Interactions of Graphene Oxide and Few-Layer Graphene with the Blood–Brain Barrier

Advanced Nanosystems for Cancer Therapeutics: A Review

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

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