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Increased Pro-Apoptotic and Anti-Proliferative Activities of Simvastatin Encapsulated PCL-PEG Nanoparticles on Human Breast Cancer Adenocarcinoma Cells

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Abstract

Recently, Simvastatin (SIM) is received notable attention due to its anti-cancer properties. However, the lipophilicity feature of SIM restricted its application as a chemotherapy agent. This work aimed to investigate the Polycaprolactone–Polyethylene Glycol (PCL-PEG) efficiency as the nano-carrier for SIM to enhance its anti-cancer properties. Dynamic Light Scattering (DLS), field emission scanning electron microscopy (FE-SEM), and Fourier transform infrared (FTIR) were used to characterize drug-loaded nanoparticles (NPs). To study apoptotic and anti-proliferative properties of drug-loaded NPs, flow cytometry and MTT assays were utilized. The real-time PCR method measured the expression of apoptotic genes Bcl-2, Bax, Fas and cell cycle regulating genes, p53, cyclin D, and Rb. MTT assay indicated that loading SIM on PCL-PEG NPs increased cytotoxicity dose-dependently. In addition, a noticeable increase was found in the sub- G1 population of treated cells with drug-loaded NPs than free SIM. The remarkable up-regulation of Bax, Fas and p53 genes was detected in treated MCF-7 cells with the decrease of Bcl2, Rb, and Cyclin D 1 gene expression in cells treated with drug-loaded NPs than free SIM. Taken together, these results show that the polymeric PCL-PEG NPs systems represent a promising new therapeutic approach for the treatment of breast cancer.

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Acknowledgements

The authors express their sincere thanks to the pharmaceutical sciences research center of Ardabil University of Medical Sciences for financial support.

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Authors and Affiliations

  1. Department of Medical Biotechnology, Semnan University of Medical Sciences, Semnan, Iran

    Mehdi Dadashpour

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

    Mehdi Dadashpour

  3. Advanced Therapy Medicinal Product Technology Development Center, Royan Institute for Stem Cell Biology and Technology, Academic Center for Education, Culture and Research, Tehran, Iran

    Meysam Ganjibakhsh

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

    Hanieh Mousazadeh

  5. Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences, Ardabil, Iran

    Kazem Nejati

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  1. Mehdi Dadashpour
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  2. Meysam Ganjibakhsh
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  3. Hanieh Mousazadeh
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  4. Kazem Nejati
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Contributions

The conception and the design of the study were performed by KN. The experiments were carried out by all authors. Data collection and analyses were conducted by MG and MD. The project was supervised by KN. The manuscript was drafted by MD, and revised by KN. All authors participated in the manuscript in the critical review process of the manuscript and approval of the final version.

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Correspondence to Kazem Nejati.

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Dadashpour, M., Ganjibakhsh, M., Mousazadeh, H. et al. Increased Pro-Apoptotic and Anti-Proliferative Activities of Simvastatin Encapsulated PCL-PEG Nanoparticles on Human Breast Cancer Adenocarcinoma Cells. J Clust Sci 34, 211–222 (2023). https://doi.org/10.1007/s10876-021-02217-y

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