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Targeted nanostructured lipid carrier containing galangin as a promising adjuvant for improving cytotoxic effects of chemotherapeutic agents

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Abstract

Resistance to chemotherapeutic drugs is the main limitation of cancer therapy. The combination use of chemotherapeutic agents and galangin (a naturally active flavonoid) amplifies the effectiveness of cancer treatment. This study aimed to prepare arginyl-glycyl-aspartic acid (RGD) containing nanostructured lipid carrier (NLC-RGD) to improve the bioavailability of galangin and explore its ability in improving the cytotoxic effects of doxorubicin (DOX). Galangin-loaded NLC-RGD was prepared by hot homogenization method and characterized by diverse techniques. Then, cytotoxicity, uptake, and apoptosis induction potential of prepared nanoparticles beside the DOX were evaluated on A549 lung cancer cells. Finally, the expression level of some ABC transporter genes was evaluated in galangin-loaded NLC-RGD-treated cells. Nanoparticles with appropriate characteristics of the delivery system (size: 120 nm, polydispersity index: 0.23, spherical morphology, and loading capacity: 59.3 mg/g) were prepared. Uptake experiments revealed that NLC-RGD promotes the accumulation of galangin into cancerous cells by integrin-mediated endocytosis. Results also showed higher cytotoxicity and apoptotic effects of DOX + galangin-loaded NLC-RGD in comparison to DOX + galangin. Gene expression analysis demonstrated that galangin-loaded NLC-RGD downregulates ABCB1, ABCC1, and ABCC2 more efficiently than galangin. These findings indicated that delivery of galangin by NLC-RGD makes it an effective adjuvant to increase the efficacy of chemotherapeutic agents in cancer treatment.

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Data generated during this study are included in the supplementary material.

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Acknowledgements

Thanks to guidance and advice from the “Clinical Research Development Unit of Baqiyatallah Hospital.”

Funding

Project was supported by the Nanobiotechnology Research Center of Baqiyatallah University of Medical Sciences (project number: 98000453, IR.BMSU.REC.1399.202).

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Authors and Affiliations

  1. Nanobiotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

    Hamed Hajipour & Ramezan Ali Taheri

  2. Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

    Mohammad Nouri

  3. Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Marjan Ghorbani

  4. Trauma Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

    Ali Bahramifar

  5. Department of Energy and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran

    Reza Zolfaghari Emameh

Authors
  1. Hamed Hajipour
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  2. Mohammad Nouri
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  3. Marjan Ghorbani
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  4. Ali Bahramifar
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  5. Reza Zolfaghari Emameh
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  6. Ramezan Ali Taheri
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Contributions

HH, RT, and MG conceived and designed research. HH, MN, and MG conducted experiments. MN and RZE provided setups and reagents/samples. AB and RZE analyzed data. HH and AB wrote the manuscript. MG revised the manuscript. RT supervised the study. All authors read and approved the manuscript, all data were generated in-house, and no paper mill was used.

Corresponding author

Correspondence to Ramezan Ali Taheri.

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Procedure of study was approved by the Ethical Committee of Baqiyatallah University of Medical Sciences (IR.BMSU.REC.1399.202).

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The authors declare no competing interests.

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Hajipour, H., Nouri, M., Ghorbani, M. et al. Targeted nanostructured lipid carrier containing galangin as a promising adjuvant for improving cytotoxic effects of chemotherapeutic agents. Naunyn-Schmiedeberg's Arch Pharmacol 394, 2353–2362 (2021). https://doi.org/10.1007/s00210-021-02152-9

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  • DOI: https://doi.org/10.1007/s00210-021-02152-9

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