Magnetically Directed Enzyme/Prodrug Prostate Cancer Therapy Based on β-Glucosidase/Amygdalin
| Autor: | Jie Zhou, Yunlong Liu, Jun Rao, Jing Hou, Conghui Zhou, Wenxi Gao |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Combination therapy
medicine.medical_treatment Cell Biophysics Pharmaceutical Science Bioengineering 02 engineering and technology 010402 general chemistry 01 natural sciences Targeted therapy Biomaterials Prostate cancer In vivo Drug Discovery PEG ratio medicine biology Chemistry Organic Chemistry General Medicine Prodrug 021001 nanoscience & nanotechnology medicine.disease Enzyme assay 0104 chemical sciences medicine.anatomical_structure Cancer research biology.protein 0210 nano-technology |
| Zdroj: | International Journal of Nanomedicine. 15:4639-4657 |
| ISSN: | 1178-2013 |
| Popis: | Background 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. |
| Databáze: | OpenAIRE |
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