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Preparation of MnO2@poly-(DMAEMA-co-IA)-conjugated methotrexate nano-complex for MRI and radiotherapy of breast cancer application

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Abstract

Objective

A novel efficient pH-sensitive targeted magnetic resonance imaging (MRI) contrast agent and innovative radio-sensitizing system were synthesized based on MnO2 NPs coated with biocompatible poly-dimethyl-amino-ethyl methacrylate-Co-itaconic acid, (DMAEMA-Co-IA) and targeted with methotrexate (MTX).

Materials and methods

The as-established NPs were fully characterized and evaluated for MRI signal enhancement, relaxivity, in vitro cell targeting, cell toxicity, blood compatibility, and radiotherapy (RT) efficacy.

Results

The targeted NPs MnO2@Poly(DMAEMA-Co-IA) and MTX-loaded NPs inhibited MCF-7 cell viability more effectively than free MTX after 24 and 48 h, respectively, with no noticeable toxicity. Additionally, the insignificant hemolytic activity demonstrated their proper hemo-compatibility. T1-weighted magnetic resonance imaging was used to distinguish the differential uptake of the produced MnO2@Poly(DMAEMA-Co-IA)-MTX NPs in malignant cells compared to normal ones in the presence of high and low MTX receptor cells (MCF-7 and MCF-10A, respectively). In MRI, the produced theranostic NPs displayed pH-responsive contrast enhancement. As shown by in vitro assays, treatment of cells with MnO2@Poly(DMAEMA-Co-IA)-MTX NPs prior to radiotherapy in hypoxic conditions significantly enhanced therapeutic efficacy.

Conclusion

We draw the conclusion that using MnO2@Poly(DMAEMA-Co-IA)-MTX NPs in MR imaging and combination radiotherapy may be a successful method for imaging and radiation therapy of hypoxia cells.

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Data cannot be shared openly but are available on request.

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Acknowledgements

This work was supported by the Medical Radiation Sciences Research Team, Tabriz University of Medical Sciences, Tabriz, Iran.

Funding

This study has been produced from a research under the title “Application of polyitaconic acid-coated manganese oxide nano-composite conjugated with methotrexate in magnetic resonance imaging and radiotherapy”, funded by the deputy of Research of Tabriz University of Medical Sciences, Tabriz, Iran (Grant # 68822) under the research ethics certificate ID: IR. TBZMED. REC.1400.1203.

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Authors and Affiliations

  1. Department of Medical Physics, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Saba Ziyaee, Reza Malekzadeh & Tohid Mortezazadeh

  2. Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Marjan Ghorbani

  3. Department of Radio-Oncology, Shahid Madani Hospital, Tabriz, Iran

    Behnam Nasiri Motlagh

  4. Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran

    Vahid Asghariazar

  5. Deputy of Research and Technology, Ardabil University of Medical Sciences, Ardabil, Iran

    Vahid Asghariazar

  6. Medical Radiation Sciences Research Team, Tabriz University of Medical Sciences, Tabriz, Iran

    Tohid Mortezazadeh

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  1. Saba Ziyaee
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  2. Reza Malekzadeh
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  3. Marjan Ghorbani
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  4. Behnam Nasiri Motlagh
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Contributions

SZ: Acquisition of data, Synthesis of NPs, drafting of manuscript; RM: Acquisition of data, analysis and interpretation of data, drafting of manuscript; MG: Preparation and synthesis of NPs, study conception and design, review of manuscript; BN: Cooperation in radiation therapy; VA: Cooperation in cellular work; TM: Supervisor of study, analysis and interpretation of data, editing and critical revision of manuscript. All authors discussed the results and contributed to the final manuscript.

Corresponding author

Correspondence to Tohid Mortezazadeh.

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The authors do not have any conflict of interest.

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Research ethics certificate ID: IR. TBZMED. REC.1400.1203.

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Ziyaee, S., Malekzadeh, R., Ghorbani, M. et al. Preparation of MnO2@poly-(DMAEMA-co-IA)-conjugated methotrexate nano-complex for MRI and radiotherapy of breast cancer application. Magn Reson Mater Phy 36, 779–795 (2023). https://doi.org/10.1007/s10334-023-01091-1

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