Graphene Nanocomposites in the Targeting Tumor Microenvironment: Recent Advances in TME Reprogramming
Abstract
1. Introduction
2. Graphene-Based Nanocomposites in the Reprogramming of the TME
2.1. Graphene and Graphene Quantum Dots
Carrier Type | Agent | Characteristics | Ref |
---|---|---|---|
GQDs Carboxylated-GQDs | - | increased membrane fluidity reduced formation of neurospheres in U87MG glioblastoma cancer cells and glioblastoma neurospheres | [57] |
Carboxylated-GQDs | DOX, TMZ | synergistic PTT on 3D spheroid model of glioblastoma, elevated intracellular ROS production, increased membrane permeability, elevated presence of tumor-associated antigens | [59] |
nitrogen-doped GQD with HA and Fc | HA, Fc | CD44 cancer cell receptor targeting in HeLa cells, Fc facilitated a redox-based toxicity by the redox cycle of iron, oxidative stress targeting | [61] |
nitrogen-doped GQD | TPP, ruthenium nitrosyl | mitochondria targeting, PTT, regulation of oxygen consumption and ATP synthesis, an inhibitory effect in the ETC, inhibited the in vivo tumor growth | [66] |
GQDs-PEI | TPP | in vitro mitochondria monitoring | [70] |
Hybrid GQDs-UCNP | TRITC | promoted increased in situ cytotoxic ROS formation, mitochondria dysfunction, decrease in mitochondria membrane potential, activation of caspase-3 apoptotic pathway | [71] |
Graphene | GA | promoted the depletion of MMP, decreased the intracellular level of lipid droplets, induced DNA fragmentation | [74] |
Pristine graphene | - | promote apoptotic mitochondria pathway signaling in murine RAW 264.7 macrophages, triggered increased ROS levels, activated Bcl-2 family pro-apoptotic proteins, activated MAPK and TGF-β signaling, activated caspace-3-related apoptotic pathway | [78] |
2.2. Graphene Oxide
Carrier Type | Agent | Characteristics | Ref |
---|---|---|---|
GO-PEG | HY, DOΧ | Combined PDT and anticancer therapy, internalization via endocytosis, glutathione-triggered HY release, pH-triggered DOX release, HY-triggered generation of singlet oxygen in mitochondria, cytochrome c release into the cytosol, caspases activation | [79] |
GO-DSPE-PEG2000 | TPP+, IR820 NIR Photosensitizer, CpG ODN | combined PDT/PTT and immunostimulatory anticancer effect, mitochondrial targeting, increased ROS production, mitochondrial induced cell death, upregulation of proinflammatory cytokines (IL-6, TNF-α, INF-γ) | [85] |
GO-ICG | TPPB | increased mitochondrial accumulation, synergistic PDT/PTT, elevated ROS (1O2, O2−) production, GO hyperthermia effect, inhibition of ATP synthesis | [88] |
GO-PEG | integrin αvβ3 mAb, PPa | on/off phototoxicity switches, FRET mechanism, mitochondria accumulation, localized ROS formation, promoting cell apoptosis | [90] |
GO-MitP | MTX | Increased mitochondria localization, promoting mitochondria dysfunction upon AFM, decrease in MMP, downregulation in ATP expression levels, cytochrome c release, activation of caspase 3 apoptotic pathway | [91] |
GO-β-CD/Plys/PEG/MitP | TPM-Azo, TF | Increased mitochondria accumulation, stimulating mitochondrial aggregation, reducing ATP levels, disruption of cancer cells cycle, arrest at the G2 phase, decreased cell viability, increased cytochrome c expression into the cytosol | [94] |
GO-GA | DOX | mitochondria targeting, selective pH-dependent DOX release, decreased the MMP, opening of the mitochondrial permeability transition pores, increase in the ratio of Bax/Bcl-2 proteins, activation of caspase-mediated apoptotic pathway | [96] |
GO-GE11 | Ori | promoted mitochondrial dysfunction, decreased the MMP, induced cell cycle arrest increasing the G2/M phase, downregulation of the Ras/Raf/MEK/ERK pathways | [101] |
GO-CSCs | - | surface-level interaction, the inhibition of key signaling pathways Wnt, Notch, and STAT3, suppression of the NRF2-dependent antioxidant response | [106] |
GO-MSCs | DOX, MTX | pH-responsive drug release, enhanced CXCR4 expression, induced cytotoxicity in glioblastoma and breast cancer cells | [107] |
AuNP/GO-MSCs | - | amplified photothermal effects upon NIR, increase in photothermal ablation efficacy, tumor-homing capacity | [108] |
2.3. Reduced Graphene Oxide
Carrier Type | Agent | Characteristics | Ref |
---|---|---|---|
rGO | - | stimulated autophagy and cell cycle arrest in cancer cells, promoted apoptosis signaling pathway, decreased the MMP, activated caspase-9 and caspase-3 cytosolic expression | [111] |
rGO | Gamma irradiation | oxidative stress damage, elevated levels of ROS expression, damage of myocardial tissue, reduced expression levels of enzymes | [112] |
rGO-MNPs | 4-HC, CMP | Combined chemophotodynamic effect, elevated ROS production, regulation of apoptotic cell death, cell shrinkage and nuclear fragmentation, increased expression of p53 and Bax proteins | [113] |
rGO | MG-132 | increased apoptosis and necrosis of breast cancer cells, increasing ROS formation, caspase-8 and caspase-9 apoptotic pathways activation, reduced enzymatic antioxidants activity (SOD, GPx) | [114] |
rGO-AgNPs | - | Decreased viability and cell growth, leakage of intracellular LDH, damage of cellular membrane integrity, ROS generation, increased MDA pro-oxidant levels, decreased antioxidant GSH production, activation of caspase-3 apoptotic death | [119] |
rGO-AgNPs | Cis | Inhibition of viability and proliferation, increased Cis-induced ROS expression levels, increased oxidative stress, elevated MDA expression levels, loss of MMP, upregulation of apoptotic genes, downregulation of anti-apoptotic genes | [120] |
rGO-Arg/Pro | - | increased cellular membranes adhesion, reduced cell proliferation, downregulation of VEGF expression, caspsase-3 activation, inhibition of FGF2, regulation of apoptosis | [123] |
3. Discussion
4. Conclusions
5. Future Directions
Funding
Conflicts of Interest
References
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Kolokithas-Ntoukas, A.; Mouikis, A.; Angelopoulou, A. Graphene Nanocomposites in the Targeting Tumor Microenvironment: Recent Advances in TME Reprogramming. Int. J. Mol. Sci. 2025, 26, 4525. https://doi.org/10.3390/ijms26104525
Kolokithas-Ntoukas A, Mouikis A, Angelopoulou A. Graphene Nanocomposites in the Targeting Tumor Microenvironment: Recent Advances in TME Reprogramming. International Journal of Molecular Sciences. 2025; 26(10):4525. https://doi.org/10.3390/ijms26104525
Chicago/Turabian StyleKolokithas-Ntoukas, Argiris, Andreas Mouikis, and Athina Angelopoulou. 2025. "Graphene Nanocomposites in the Targeting Tumor Microenvironment: Recent Advances in TME Reprogramming" International Journal of Molecular Sciences 26, no. 10: 4525. https://doi.org/10.3390/ijms26104525
APA StyleKolokithas-Ntoukas, A., Mouikis, A., & Angelopoulou, A. (2025). Graphene Nanocomposites in the Targeting Tumor Microenvironment: Recent Advances in TME Reprogramming. International Journal of Molecular Sciences, 26(10), 4525. https://doi.org/10.3390/ijms26104525