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Global Translational Medicine Graphene oxide in cancer drug delivery applications

5. Effects of GO and rGO on immune tumor infiltration in vivo. These T-cells precisely targeted
response and attacked PD-L1-suppressed glioma cells, promoting a
robust anti-tumor immune reaction induced by PTT in a
On introduction into the body, peripheral immune syngeneic mouse model of glioblastoma subcutaneously
cells in the blood or peripheral tissues quickly interact implanted with ALTS1C1 cells. 75
with graphene-based compounds such as GO and rGO,
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triggering an immunological response. GO has been A study conducted by Deng et al. 70,76 revealed that
shown to induce the generation of reactive oxygen species the macrophage cell line RAW264.7, when exposed to
in diverse immune cells, potentially altering biological IL-4 and GO in combination with PEG and NIR light,
macromolecules. As a result, the treatment of cancer cells exhibited a reduction in M2 macrophages. In addition,
with GO reduces their viability by inducing cytotoxic the researchers co-cultured human osteosarcoma cells
effects through DNA damage. These findings highlight GO’s with macrophages and injected these cells into nude mice.
After tumor development, a combination of GO and PEG
potential as an effective drug carrier capable of penetrating was administered, followed by the application of PTT. The
the tumor microenvironment and directly destroying findings indicated that tumor size in mice treated with GO
tumor cells. 69,70
combined with PEG and NIR irradiation was diminished,
Another study indicates that murine peritoneal accompanied by the suppression of anti-apoptotic factors
macrophages exposed to GO nanosheets modified with such as Bcl-2 and the activation of pro-apoptotic proteins
poly(ethylene glycol-amine) and labeled with fluorescein such as caspase-3 and Bax. This treatment also led to a
isothiocyanate (FITC-PEG-GO) experienced a substantial decrease in anti-inflammatory M2 macrophages and an
reduction in the percentage of anti-inflammatory M2 increase in pro-inflammatory M1 macrophages. 70,76 The
macrophages (CD206 ), which are often associated with effects of rGO on lung cancer cell lines A549 and SKMES-1
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tumors, following 24 and 48 h. 70,71 In addition, GO has the were also investigated. Results indicated that low levels of
capacity to absorb anti-interleukin (IL)-10R antibodies rGO predominantly induced late apoptosis and necrosis,
and interferon‐gamma (IFN-γ). The combination of GO, rather than early apoptotic events, in both cell lines. 70,77
anti-IL-10R, and IFN-γ (GO-anti-IL-10R-IFN-γ) induces
a strong Th1 immune response in vitro. Interestingly, 6. Conclusion and future perspectives
immunization of mice with GO-anti-IL-10R-IFN-γ resulted Advancements in the modification of GO-based
in robust ovalbumin (OVA)-specific CD8 T-cell responses, nanomaterials have resulted in the development of versatile
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which effectively inhibited tumor development. 72 nanocomposites with both diagnostic and therapeutic
Another in vivo investigation demonstrated that OVA- properties. These nanocomposites show great potential as
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loaded rGO-dextran induced cytotoxic T lymphocytes platforms for comprehensive cancer treatment. Despite
and suppressed tumor growth. In a separate study, their promising applications, GO and rGO still require
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it was reported that pegylated GO nanoparticles at a further investigation before widespread clinical use can be
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concentration of 10 μg/mL inhibited the differentiation of achieved. Key concerns include biocompatibility, long-
human myeloid-derived suppressor cells (MDSCs) in vitro, term safety, and efficient tumor targeting, all of which
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potentially impeding cancer progression due to the pro- demand extensive study. Further investigation is crucial
carcinogenic nature of MDSCs. 69,74 to enhance the pharmacokinetics, biodistribution, and
therapeutic effectiveness of these nanomaterials, ensuring
Lu et al. developed a nanovehicle comprising rGO their safe and effective use in human patients. Moreover,
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quantum dots (rGOQDs) loaded with resiquimod (R848), a more detailed understanding of the interactions between
an immunomodulatory drug, and coupled with an anti- GO-based materials and biological systems at the molecular
PD-L1 antibody (aPD-L1). The rGOQD/R8/aPDL1 level is critical for the development of more precise and
nanoparticles specifically targeted PD-L1 on the surface of effective cancer treatments. Despite current limitations,
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ALTS1C1 murine glioblastoma cells, while the release of GO and rGO exhibit enormous prospects for cancer therapy
R848 augmented the T-cell-mediated anti-tumor response. and diagnostics due to their exceptional properties. Notably,
In vitro studies following NIR irradiation demonstrated GO and rGO are recognized as effective photothermal
that PD-L1-mediated intracellular uptake and the rGOQD- agents, due to their strong NIR absorption and photothermal
induced photothermal response resulted in cancer cell conversion capabilities. These capabilities suggest their
death, along with the release of damage-associated potential application in PTT, either independently or in
molecular patterns (DAMPs). The synergistic effect of conjunction with other therapeutic approaches for cancer
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R848 and the released DAMPs generated antigens that therapy. Furthermore, these nanomaterials offer numerous
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activated dendritic cells, thereby priming T lymphocytes for benefits over other drug delivery systems, including a

Volume 3 Issue 3 (2024) 7 doi: 10.36922/gtm.4602