International Journal of Nanomedicine (Jun 2020)
Magnetically Directed Enzyme/Prodrug Prostate Cancer Therapy Based on β-Glucosidase/Amygdalin
Abstract
Jie Zhou,1,2 Jing Hou,1,2 Jun Rao,2,3 Conghui Zhou,2,4 Yunlong Liu,5 Wenxi Gao1,2 1Department of Urology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, Hubei, People’s Republic of China; 2Hubei Province Academy of Traditional Chinese Medicine, Wuhan, Hubei, People’s Republic of China; 3Clinical Laboratory, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, Hubei, People’s Republic of China; 4Department of Pharmaceutical Sciences, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, Hubei, People’s Republic of China; 5Department of Urology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Jie Zhou Email [email protected]: β-Glucosidase (β-Glu) can activate amygdalin to kill prostate cancer cells, but the poor specificity of this killing effect may cause severe general toxicity in vivo, limiting the practical clinical application of this approach.Materials and Methods: In this study, starch-coated magnetic nanoparticles (MNPs) were successively conjugated with β-Glu and polyethylene glycol (PEG) by chemical coupling methods. Cell experiments were used to confirm the effects of immobilized β-Glu on amygdalin-mediated prostate cancer cell death in vitro. Subcutaneous xenograft models were used to carry out the targeting experiment and magnetically directed enzyme/prodrug therapy (MDEPT) experiment in vivo.Results: Immobilized β-Glu activated amygdalin-mediated prostate cancer cell death. Tumor-targeting studies showed that PEG modification increased the accumulation of β-Glu-loaded nanoparticles in targeted tumor tissue subjected to an external magnetic field and decreased the accumulation of the nanoparticles in the liver and spleen. Based on an enzyme activity of up to 134.89 ± 14.18mU/g tissue in the targeted tumor tissue, PEG-β-Glu-MNP/amygdalin combination therapy achieved targeted activation of amygdalin and tumor growth inhibition in C57BL/6 mice bearing RM1 xenografts. Safety evaluations showed that this strategy had some impact on liver and heart function but did not cause obvious organ damage.Conclusion: All findings indicate that this magnetically directed enzyme/prodrug therapy strategy has the potential to become a promising new approach for targeted therapy of prostate cancer.Keywords: magnetic nanoparticles, β-glucosidase, amygdalin, prostate cancer, magnetically directed enzyme/prodrug therapy
