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Transferrin Immobilized Graphene Oxide Nanocomposite for Targeted Cancer Chemodynamic Therapy via Increasing Intracellular Labile Fe2+ Concentration
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    Transferrin Immobilized Graphene Oxide Nanocomposite for Targeted Cancer Chemodynamic Therapy via Increasing Intracellular Labile Fe2+ Concentration
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    • Ashish K Shukla
      Ashish K Shukla
      Biotechnology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh 176061, India
      Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
    • Mohini Verma
      Mohini Verma
      Biotechnology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh 176061, India
      Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
      More by Mohini Verma
    • Manik Bathla
      Manik Bathla
      Biotechnology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh 176061, India
      Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
      More by Manik Bathla
    • Shiwani Randhawa
      Shiwani Randhawa
      Biotechnology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh 176061, India
      Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
    • Trilok Chand Saini
      Trilok Chand Saini
      Biotechnology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh 176061, India
      Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
    • Avnesh Kumari
      Avnesh Kumari
      Biotechnology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh 176061, India
      Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
    • Amitabha Acharya*
      Amitabha Acharya
      Biotechnology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh 176061, India
      Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
      *Email: [email protected], [email protected]; Tel. (Office): +91-1894-233339, Ext. 397; Fax: +91-1894-230433.
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    ACS Applied Bio Materials

    Cite this: ACS Appl. Bio Mater. 2024, 7, 6, 3649–3659
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    https://doi.org/10.1021/acsabm.3c01147
    Published May 10, 2024
    Copyright © 2024 American Chemical Society

    Abstract

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    Recently, different alternative regulated cell death (RCD) pathways, viz., necroptosis, pyroptosis, ferroptosis, cuproptosis etc., have been explored as important targets for the development of cancer medications in recent years, as these can change the immunogenicity of the tumor microenvironment (TME) and will finally lead to the inhibition of cancer progression and metastasis. Here, we report the development of transferrin immobilized graphene oxide (Tfn@GOAPTES) nanocomposite as a therapeutic strategy toward cancer cell killing. The electrostatic immobilization of Tfn on the GOAPTES surface was confirmed by different spectroscopy and microscopy techniques. The Tfn immobilization was found to be ∼74 ± 4%, whereas the stability of the protein on the GO surface suggested a robust nature of the nanocomposite. The MTT assay suggested that Tfn@GOAPTES exhibited cytotoxicity toward HeLa cells via increased lipid peroxidation and DNA damage. Western blot studies resulted in decreased expression of acetylation on lysine 40 of α-tubulin and increased expression of LC3a/b for Tfn@GOAPTES treated HeLa cells, suggesting autophagy to be the main cause of the cell death mechanism. Overall, we predict that the present approach can be used as a therapeutic strategy for cancer cell killing via selective induction of a high concentration of intracellular iron.

    Copyright © 2024 American Chemical Society

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    Supporting Information

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsabm.3c01147.

    • Experimental section, cellular studies, CD-studies, XPS-studies, TGA-DSC studies, TEM & SEM studies, colloidal stability studies, cytocompatibility assay, total thiol estimation, perl’s prussian blue staining assay (PDF)

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    This article is cited by 2 publications.

    1. Mohini Verma, Shiwani Randhawa, Manik Bathla, Nandini Teji, Amitabha Acharya. Strategic use of nanomaterials as double-edged therapeutics to control carcinogenesis via regulation of dysbiosis and bacterial infection: current status and future prospects. Journal of Materials Chemistry B 2025, 13 (16) , 4770-4790. https://doi.org/10.1039/D4TB02409E
    2. Nem Singh, Dahee Kim, Sunhong Min, Eunji Kim, Shiyoung Kim, Yu Shrike Zhang, Heemin Kang, Jong Seung Kim. Multimodal synergistic ferroptosis cancer therapy. Coordination Chemistry Reviews 2025, 522 , 216236. https://doi.org/10.1016/j.ccr.2024.216236

    ACS Applied Bio Materials

    Cite this: ACS Appl. Bio Mater. 2024, 7, 6, 3649–3659
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acsabm.3c01147
    Published May 10, 2024
    Copyright © 2024 American Chemical Society

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