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Smac Gene Delivery by the Glycol Chitosan with Low Molecular Weight Polyethylenimine Induces Apoptosis of Cancer Cells for Combination Therapy with Etoposide

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Abstract

We developed polymer-based nanoparticle carriers for gene delivery, glycol chitosan (GC)-methyl acrylate-low molecular weight polyethylenimine (800Da PEI), GMP, and investigated their ability to deliver second mitochondria-activation of caspase (Smac) gene into cancer cell lines. We analyzed cytotoxicity level and gene transfection efficiency in GBL-14, U373-MG, MDA-MB-231, and dermal fibroblasts (HDF) cell lines. GMP exhibited significantly lower cytotoxicity level, as compared with PEI25KD. Also, it showed high transfection efficiency in these cell lines. We treated these cells with a complex of GMP and Smac, and investigated their facilitated cellular uptake by flow cytometry. Also, analyses using cell cycle distribution, Annexin V staining, JC-1, and caspase-3 activity, indicated that apoptosis was induced by GMP/FLAG-Smac combined with etoposide in MDA-MB-231 cell line. This study demonstrates that combining the GMP/FLAG-Smac complex with chemotherapeutic agents could potentially be an effective approach for cancer therapy.

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Correspondence to Jin Han or Joon Sig Choi.

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Acknowledgments: This work was supported by grant from Basic Science Research Program through the National Research Foundation of Korea (NRF-2016R1D1A1A09917141) and by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (NRF-2018M3A9B5024060 and NRF-2018M3A9B5024068). This work was also supported by the Priority Research Centers Program (2010-0020224).

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Bae, Y., Lee, Y.H., Ko, K.S. et al. Smac Gene Delivery by the Glycol Chitosan with Low Molecular Weight Polyethylenimine Induces Apoptosis of Cancer Cells for Combination Therapy with Etoposide. Macromol. Res. 27, 944–954 (2019). https://doi.org/10.1007/s13233-019-7130-4

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