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Cisplatin and farnesol co-encapsulated PLGA nano-particles demonstrate enhanced anti-cancer potential against hepatocellular carcinoma cells in vitro

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Abstract

Cisplatin (CDDP) is a potent chemotherapeutic drug, but its severe side-effects often prohibit its use. Combined treatment with CDDP plus Farnesol (FAR) and their co-encapsulated nano form were investigated in in vitro to examine if synergistic cytotoxicity of this combination could reduce unwanted side-effects of CDDP chemotherapy and potentiate CDDP anticancer activity against hepatocellular carcinoma (HCC) cells. After finding combination therapy of CDDP and FAR successfully combat HCC we formulated co-encapsulation of CDDP and FAR within poly(lactic-co-glycolic acid) copolymer (NCDDPFAR) by following the standardized solvent displacement method. NCDDPFAR treatment caused faster drug mobility, sustained particle release, site-specific action and higher percentage of apoptotic death compared with single drug treatment even at relatively low concentrations. Co-encapsulation of two drugs exhibited additive effects against HCC; FAR reduced CDDP-induced glutathione level by increasing expression of CYP2E1 while CDDP directly interacted with DNA; FAR up-regulated the expression of TopII, thereby promoting DNA breaks and escaping DNA repair machinery. Expression pattern of apoptotic genes like p53, Bax, cytochrome c and caspase-3 suggested that NCDDPFAR induced HCC cell death through mitochondrial intrinsic pathway. Administration of NCDDPFAR had better ability of drug carriage and enhanced anticancer potentials against HCC cells.

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Acknowledgements

We are very much indebted to Prof. Ashish Kumar Panigrahi, Head, Department of Zoology, University of Kalyani (KU), for his encouragements and help. Thanks also go to Dr. Mousumi Patra, Department of Biochemistry and Biophysics, KU for DLS spectroscopy. We extend our sincere thanks to IACS, India for CD spectroscopy.

Funding

This work was supported by University of Grants Commission, New Delhi, India [Grant No. F1-17.1/2012-13/MANF-2012-13-MUS-WES-13662, 2013].

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  1. Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, Kalyani, 741235, India

    Jesmin Mondal & Anisur Rahman Khuda-Bukhsh

  2. B-2/325, Kalyani, 741235, India

    Anisur Rahman Khuda-Bukhsh

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Mondal, J., Khuda-Bukhsh, A.R. Cisplatin and farnesol co-encapsulated PLGA nano-particles demonstrate enhanced anti-cancer potential against hepatocellular carcinoma cells in vitro. Mol Biol Rep 47, 3615–3628 (2020). https://doi.org/10.1007/s11033-020-05455-x

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