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.



中文翻译：

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基于β-葡萄糖苷酶/苦杏仁苷的磁性定向酶/前药前列腺癌治疗。

背景： β-葡萄糖苷酶（β-Glu）可以激活苦杏仁苷杀死前列腺癌细胞，但这种杀伤作用的特异性较差，可能会导致体内严重的全身毒性，限制了该方法的实际临床应用。
材料与方法：在本研究中，淀粉包覆的磁性纳米粒子（MNPs）通过化学偶联方法与β-Glu和聚乙二醇（PEG）连续偶联。细胞实验用于证实固定化 β-Glu 对苦杏仁苷介导的体外前列腺癌细胞死亡的影响。使用皮下异种移植模型进行体内靶向实验和磁定向酶/前药治疗（MDEPT）实验。
结果：固定化 β-Glu 激活苦杏仁苷介导的前列腺癌细胞死亡。肿瘤靶向研究表明，PEG修饰增加了负载β-Glu的纳米颗粒在外磁场作用下的靶向肿瘤组织中的积累，并减少了纳米颗粒在肝脏和脾脏中的积累。基于靶向肿瘤组织中高达 134.89 ± 14.18mU/g 组织的酶活性，PEG-β-Glu-MNP/苦杏仁苷联合疗法在携带 RM1 异种移植物的 C57BL/6 小鼠中实现了苦杏仁苷的靶向激活和肿瘤生长抑制。安全性评估表明，该策略对肝脏和心脏功能有一定影响，但未造成明显的器官损害。
结论：所有研究结果表明，这种磁性定向酶/前药治疗策略有可能成为前列腺癌靶向治疗的一种有前途的新方法。