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Characterization of ginsenoside compound K loaded ionically cross-linked carboxymethyl chitosan-calcium nanoparticles and its cytotoxic potential against prostate cancer cells

  • Zhang, Jianmei (Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental protection, Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University) ;
  • Zhou, Jinyi (Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental protection, Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University) ;
  • Yuan, Qiaoyun (Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental protection, Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University) ;
  • Zhan, Changyi (Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental protection, Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University) ;
  • Shang, Zhi (Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental protection, Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University) ;
  • Gu, Qian (Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental protection, Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University) ;
  • Zhang, Ji (Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental protection, Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University) ;
  • Fu, Guangbo (Department of Urology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University) ;
  • Hu, Weicheng (Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental protection, Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University)
  • Received : 2019.06.02
  • Accepted : 2020.01.30
  • Published : 2021.03.01

Abstract

Backgroud: Ginsenoside compound K (GK) is a major metabolite of protopanaxadiol-type ginsenosides and has remarkable anticancer activities in vitro and in vivo. This work used an ionic cross-linking method to entrap GK within O-carboxymethyl chitosan (OCMC) nanoparticles (Nps) to form GK-loaded OCMC Nps (GK-OCMC Nps), which enhance the aqueous solubility and stability of GK. Methods: The GK-OCMC Nps were characterized using several physicochemical techniques, including x-ray diffraction, transmission electron microscopy, zeta potential analysis, and particle size analysis via dynamic light scattering. GK was released from GK-OCMC Nps and was conducted using the dialysis bag diffusion method. The effects of GK and GK-OCMC Nps on PC3 cell viability were measured by using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Fluorescent technology based on Cy5.5-labeled probes was used to explore the cellular uptake of GK-OCMC Nps. Results: The GK-OCMC NPs had a suitable particle size and zeta potential; they were spherical with good dispersion. In vitro drug release from GK-OCMC NPs was pH dependent. Moreover, the in vitro cytotoxicity study and cellular uptake assays indicated that the GK-OCMC Nps significantly enhanced the cytotoxicity and cellular uptake of GK toward the PC3 cells. GK-OCMC Nps also significantly promoted the activities of both caspase-3 and caspase-9. Conclusion: GK-OCMC Nps are potential nanocarriers for delivering hydrophobic drugs, thereby enhancing water solubility and permeability and improving the antiproliferative effects of GK.

Keywords

Acknowledgement

This study was supported financially by National Natural Science Foundation of China (31600281), Natural Science Foundation of Jiangsu Province (BK20171269), 333 Project of Jiangsu Province (BRA2017241), Natural Science Foundation of the Jiangsu Higher Education Institutions of China (18KJB320001), and Qing Lan Project of Jiangsu Province.

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