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Potentiation of Folate-Functionalized PLGA-PEG nanoparticles loaded with metformin for the treatment of breast Cancer: possible clinical application

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Abstract

Aim: Folate receptor expression increase up to 30% in breast cancer cells and could be used as a possible ligand to couple to folate-functionalized nanoparticles. Metformin (Met) is an anti-hyperglycemic agent whose anti-cancer properties have been formerly reported. Consequently, in the current study, we aimed to synthesize and characterize folate-functionalized PLGA-PEG NPs loaded with Met and evaluate the anti-cancer effect against the MDA-MB-231 human breast cancer cell line. Methods: FA-PLGA-PEG NPs were synthesized by employing the W1/O/W2 technique and their physicochemical features were evaluated by FE-SEM, TEM, FTIR, and DLS methods. The cytotoxic effects of free and Nano-encapsulated drugs were analyzed by the MTT technique. Furthermore, RT-PCR technique was employed to assess the expression levels of apoptotic and anti-apoptotic genes. Result: MTT result indicated Met-loaded FA-PLGA-PEG NPs exhibited cytotoxic effects in a dose-dependently manner and had more cytotoxic effects relative to other groups. The remarkable down-regulation (hTERT and Bcl-2) and up-regulation (Caspase7, Caspase3, Bax, and p53) gene expression were shown in treated MDA-MB-231 cells with Met-loaded FA-PLGA-PEG NPs. Conclusion: Folate-Functionalized PLGA-PEG Nanoparticles are suggested as an appropriate approach to elevate the anticancer properties of Met for improving the treatment effectiveness of breast cancer cells.

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Data Availability

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

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Acknowledgements

The research protocol was approved & Supported by Student Research Committee, Tabriz University of Medical Sciences (grant number: 65281).

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The authors declare that no funds were received during the preparation of this manuscript.

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Authors and Affiliations

  1. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran

    Davoud Jafari-Gharabaghlou

  2. Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Davoud Jafari-Gharabaghlou, Omid Joodi khanghah, Elnaz Salmani-Javan & Nosratollah Zarghami

  3. Department of Medical Biotechnology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran

    Mehdi Dadashpour

  4. Biotechnology Research Center, Semnan University of Medical Sciences, Semnan, Iran

    Mehdi Dadashpour

  5. Department of Medical Biochemistry, Faculty of Medicine, Istanbul Aydin University, Istanbul, Turkey

    Nosratollah Zarghami

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  1. Davoud Jafari-Gharabaghlou
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Contributions

Davoud Jafari-Gharabaghlou: Methodology, Investigation, Data curation, Original draft preparation.

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Correspondence to Nosratollah Zarghami.

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Mehdi Dadashpour

Methodology, Reviewing and Editing.

Omid Joodi khanghah

Methodology, Investigation, Original draft preparation.

Elnaz Salmani-Javan

Methodology, Investigation.

Nosratollah Zarghami

Supervision, Conceptualization, Writing- Reviewing and Editing.

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Jafari-Gharabaghlou, D., Dadashpour, M., khanghah, O.J. et al. Potentiation of Folate-Functionalized PLGA-PEG nanoparticles loaded with metformin for the treatment of breast Cancer: possible clinical application. Mol Biol Rep 50, 3023–3033 (2023). https://doi.org/10.1007/s11033-022-08171-w

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