Graphene Quantum Dots’ Surface Chemistry Modulates the Sensitivity of Glioblastoma Cells to Chemotherapeutics

Perini, Giordano; Palmieri, Valentina; Ciasca, Gabriele; D’Ascenzo, Marcello; Gervasoni, Jacopo; Primiano, Aniello; Rinaldi, Monica; Fioretti, Daniela Piergili; Prampolini, Chiara; Tiberio, Federica; Lattanzi, Wanda; Parolini, Ornella; Spirito, M.; Papi, Massimiliano

doi:10.3390/ijms21176301

Cited by 40 publications

(37 citation statements)

References 62 publications

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“…Viability after two weeks remained at the biocompatible levels of 94, 97 and 93% ± 6.2, 9.3 and 5.1%, respectively, at 50, 100 and 200 µg/mL ( Figure 2C). We already reported the high biocompatibility of surface-functionalized GQDs [6][7][8]. Our data are in accordance with most of the current literature.…”

Section: Biocompatibility Of Gqdssupporting

confidence: 92%

“…The reason underlying downregulation of neurospheres in GBM could be due to specific cell membrane alterations, which could affect tumor malignancy properties [7]. Proliferation and migration of neural precursor cells are indeed essential determinants of central nervous system development, as well as for the invasiveness of GBM [27].…”

Section: Membrane Fluidity Shifts In Neurospheres' Formationmentioning

confidence: 99%

“…GQDs were purchased from Sigma-Aldrich. GQDs, COOH-GQDs and NH 2 -GQDs were optically and microscopically characterized, as previously reported [6,7]. TEM measurements were performed with a Zeiss Libra 120 Transmission electron microscope (Oberkochen, Germany).…”

Section: Characterization Of Gqdsmentioning

confidence: 99%

“…In our previous studies, we investigated the effect of graphene quantum dots (GQDs) functionalized with different surface groups on glioblastoma multiforme (GBM) cell line [6][7][8]. We demonstrated the effectiveness of GQDs and carboxylated GQDs (COOH-GQDs) as enhancing agents along with the antitumor drug doxorubicin (Dox).…”

Section: Introductionmentioning

confidence: 99%

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Functionalized Graphene Quantum Dots Modulate Malignancy of Glioblastoma Multiforme by Downregulating Neurospheres Formation

Perini

Palmieri

Ciasca

et al. 2021

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Glioblastoma multiforme (GBM) is the most aggressive brain cancer. We previously demonstrated the effect of biocompatible surface functionalized graphene quantum dots (GQDs) on GBM cells as chemotherapy enhancers in combination with the antitumor drug doxorubicin (Dox). However, traditional two-dimensional cultures could not represent a reliable model of tumor behavior. In this work, we investigated the effect of carboxylated (COOH-GQDs), aminated (NH2-GQDs) and unfunctionalized GQDs on a three-dimensional model of neurospheres. Neurospheres are clusters of GBM cells, which formation is driven by the presence of a stem subpopulation involved in cancer malignancy. Tumor recurrence after surgical resection, chemotherapy and radiotherapy indeed depends on the presence of cancer cells with stem properties. We measured a significant reduction in number and size of neurospheres after two weeks of monitoring in the presence of COOH-GQDs and GQDs. Previous works pointed out how variations of membrane fluidity could affect membrane stability and cell-to-cell interactions, thus influencing cell clustering. Therefore, we measured changes in membrane fluidity after administration of GQDs. We found that COOH-GQDs and GQDs significantly increased membrane fluidity with respect to the treatment with NH2-GQDs or compared to untreated cells. Shifts in the phase of phospholipid bilayer were in accordance with the negative surface net charge of GQDs. We depicted a strong correlation between negatively charged GQDs-induced increase in membrane fluidity and the downregulation of neurospheres formation. Our results indicate that COOH-GQDs and GQDs significantly modulate tumor malignancy by increasing fluidity of cell membrane, with a consequent inhibition of cell-to-cell interaction.

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Section: Biocompatibility Of Gqdssupporting

confidence: 92%

Section: Membrane Fluidity Shifts In Neurospheres' Formationmentioning

confidence: 99%

Section: Characterization Of Gqdsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Functionalized Graphene Quantum Dots Modulate Malignancy of Glioblastoma Multiforme by Downregulating Neurospheres Formation

Perini

Palmieri

Ciasca

et al. 2021

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“…Moreover, GQDs have shown a high capability of crossing several biological barriers [13], including the BBB, both in vitro [22,23] and in vivo [24,25]. Furthermore, experimental evidence has underlined the possible use of GQDs for cancer diagnosis and drug delivery, as well as for photothermal techniques [26,27]. In this paper, we report on the effect of GQDs functionalized with dimethylformamide (DMF-GQDs), bearing an intrinsic toxicity, and of biocompatible non-functionalized GQDs (NF-GQDs), on two neural lineages: U87 GBM cells and primary mouse cortical neurons.…”

Section: Introductionmentioning

confidence: 99%

Enhanced Chemotherapy for Glioblastoma Multiforme Mediated by Functionalized Graphene Quantum Dots

et al. 2020

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Glioblastoma is the most aggressive and lethal brain cancer. Current treatments involve surgical resection, radiotherapy and chemotherapy. However, the life expectancy of patients with this disease remains short and chemotherapy leads to severe adverse effects. Furthermore, the presence of the blood–brain barrier (BBB) makes it difficult for drugs to effectively reach the brain. A promising strategy lies in the use of graphene quantum dots (GQDs), which are light-responsive graphene nanoparticles that have shown the capability of crossing the BBB. Here we investigate the effect of GQDs on U87 human glioblastoma cells and primary cortical neurons. Non-functionalized GQDs (NF-GQDs) demonstrated high biocompatibility, while dimethylformamide-functionalized GQDs (DMF-GQDs) showed a toxic effect on both cell lines. The combination of GQDs and the chemotherapeutic agent doxorubicin (Dox) was tested. GQDs exerted a synergistic increase in the efficacy of chemotherapy treatment, specifically on U87 cells. The mechanism underlying this synergy was investigated, and it was found that GQDs can alter membrane permeability in a manner dependent on the surface chemistry, facilitating the uptake of Dox inside U87 cells, but not on cortical neurons. Therefore, experimental evidence indicates that GQDs could be used in a combined therapy against brain cancer, strongly increasing the efficacy of chemotherapy and, at the same time, reducing its dose requirement along with its side effects, thereby improving the life quality of patients.

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Delivering the Promise of Gene Therapy with Nanomedicines in Treating Central Nervous System Diseases

et al. 2022

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Central Nervous System (CNS) diseases, such as Alzheimer's diseases (AD), Parkinson's Diseases (PD), brain tumors, Huntington's disease (HD), and stroke, still remain difficult to treat by the conventional molecular drugs. In recent years, various gene therapies have come into the spotlight as versatile therapeutics providing the potential to prevent and treat these diseases. Despite the significant progress that has undoubtedly been achieved in terms of the design and modification of genetic modulators with desired potency and minimized unwanted immune responses, the efficient and safe in vivo delivery of gene therapies still poses major translational challenges. Various non‐viral nanomedicines have been recently explored to circumvent this limitation. In this review, an overview of gene therapies for CNS diseases is provided and describes recent advances in the development of nanomedicines, including their unique characteristics, chemical modifications, bioconjugations, and the specific applications that those nanomedicines are harnessed to deliver gene therapies.

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Graphene Quantum Dots’ Surface Chemistry Modulates the Sensitivity of Glioblastoma Cells to Chemotherapeutics

Cited by 40 publications

References 62 publications

Functionalized Graphene Quantum Dots Modulate Malignancy of Glioblastoma Multiforme by Downregulating Neurospheres Formation

Functionalized Graphene Quantum Dots Modulate Malignancy of Glioblastoma Multiforme by Downregulating Neurospheres Formation

Enhanced Chemotherapy for Glioblastoma Multiforme Mediated by Functionalized Graphene Quantum Dots

Delivering the Promise of Gene Therapy with Nanomedicines in Treating Central Nervous System Diseases

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