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Temozolomide and Doxorubicin Combined Treatment by Graphene Oxide-Cyclodextrin Nanocarriers for Synergistic Inhibition of Glioblastoma Cells

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Abstract

Temozolomide (TMZ) is the first-line chemotherapy for glioblastoma, a deadly brain cancer. Doxorubicin (DOX) is another cancer chemotherapeutic drug, but low blood–brain barrier permeability limits its use for glioblastoma. This limitation may be overcome using nanocarriers as new delivery strategies. This study aimed to load DOX and TMZ on cyclodextrin-graphene oxide nanocarrier and evaluate their combined cytotoxic effect against glioblastoma. The α-, β-, and γ-cyclodextrins (CDs) were separately conjugated to graphene oxide (GO) sheets to synthesize nanocarriers for TMZ and DOX. The entrapment and drug loading efficiency were determined by UV–visible spectrophotometry analysis at 480 nm for TMZ and 330 nm for DOX. The MTT assay and annexin V/PI staining were used to assess cytotoxicity of TMZ, DOX, and their nanocarriers on viability and apoptosis of U87 cells. Drug-content evaluation showed that the loading efficiency of α-, β-, and γ-CD-GO-TMZ was 29%, 31%, and 21%, respectively. The loading level for DOX was found to be 18–25%. The nanocarriers loaded with TMZ and DOX showed more cytotoxic effects against glioblastoma cells compared to the drugs used alone. Among different kinds of α-, β-, and γ-CD-GO nanocarriers, the β-CD-GO-TMZ and α-CD-GO-DOX showed better cytotoxic activity. Combination of γ-CD-GO-TMZ and γ-CD-GO-DOX exhibited a synergistic effect. Also, the drug-loaded nanocarriers were able to induce apoptosis and necrosis in glioblastoma cells. In conclusion, our findings demonstrated that formulation of TMZ and DOX using CD-GO nanocarriers may be a promising candidate for glioblastoma management.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This study was supported by a research grant from the National Institutes for Medical Research Development (NIMAD), Tehran, Iran.

Author information

Authors and Affiliations

  1. Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran

    Elham Einafshar & Ahmad Ghorbani

  2. Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Elham Einafshar & Maryam Hashemi

  3. Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Maryam Hashemi

  4. Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Aida Gholoobi

  5. Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Aida Gholoobi

  6. Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Leila Mobasheri & Ahmad Ghorbani

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  1. Elham Einafshar
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  2. Maryam Hashemi
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  3. Aida Gholoobi
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  4. Leila Mobasheri
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  5. Ahmad Ghorbani
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Contributions

Elham Einafshar conducted the experiments, analyzed the data, and wrote the manuscript; , Maryam Hashemi, Aida Gholoobi and Leila Mobasheri participated in the experiments and data analysis; Ahmad Ghorbani designed and supervised the research and reviewed the manuscript. All authors read and agreed with the published version of the manuscript.

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Correspondence to Ahmad Ghorbani.

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Einafshar, E., Hashemi, M., Gholoobi, A. et al. Temozolomide and Doxorubicin Combined Treatment by Graphene Oxide-Cyclodextrin Nanocarriers for Synergistic Inhibition of Glioblastoma Cells. BioNanoSci. (2024). https://doi.org/10.1007/s12668-024-01299-y

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