基于纳米酶酶级联增效CDT/超声/ 免疫协同治疗乳腺癌的实验研究
Experimental study on the synergistic treatment of breast cancer based on nanoenzyme cascade enhancement of CDT/ ultrasound/immunotherapy
投稿时间:2026-04-12  修订日期:2026-05-12
DOI:
中文关键词:  纳米酶  化学动力疗法;超声  免疫治疗  乳腺癌  谷胱甘肽耗竭
英文关键词:Nanozyme  Chemodynamic therapy (CDT)  Ultrasound  Immunotherapy  Breast cancer  Glutathione depletion
基金项目:重庆市自然科学基金 (CSTB2024NSCQ-MSX0658)
作者单位邮编
赵紫薇 成都中医药大学 400016
卢岷* 重庆医科大学附属璧山医院 400016
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中文摘要:
      本研究构建了一种多功能纳米酶HSA-GOx-CuO,它可以通过酶级联反应自我供给H?O?,耗竭谷胱甘肽(GSH),从而增强氧化应激,激活抗肿瘤免疫。体外实验结果表明,联合超声处理后,HSA-GOx-CuO可有效消耗谷胱甘肽并提升细胞内活性氧水平(p < 0.05);同时能够促进树突状细胞成熟,其CD80?CD86?双阳性细胞比例为对照组的2.4倍(p < 0.01)。体内抑瘤实验表明,依托肿瘤组织增强渗透滞留效应,该纳米酶可有效富集于肿瘤部位,肿瘤抑制率可达92.8%,且生物相容性优异。本研究构建的级联纳米平台整合饥饿治疗与GSH耗竭策略,实现了化学动力学治疗、超声治疗及免疫治疗的协同抗肿瘤作用,为乳腺癌精准治疗提供了一种安全可行的新型纳米制剂。
英文摘要:
      This study developed a multifunctional nanoenzyme, HSA-GOx-CuO, which can self-supply H?O? and deplete glutathione (GSH) through an enzyme cascade reaction, thereby enhancing oxidative stress and activating anti-tumor immunity. In vitro experiments demonstrated that ultrasound-activated HSA-GOx-CuO effectively depleted glutathione and elevated intracellular reactive oxygen species (ROS) levels (p < 0.05). Notably, it promoted dendritic cell maturation, with the CD80?CD86? double-positive cell population increasing 2.4-fold compared to the control group (p < 0.01). In vivo tumor inhibition studies revealed effective tumor accumulation via the enhanced permeability and retention (EPR) effect, achieving an exceptional tumor suppression rate of 92.8% with excellent biocompatibility.This integrated nano-platform combines starvation therapy with glutathione depletion strategy, achieving synergistic therapeutic outcomes through combined chemodynamic therapy, sonodynamic therapy, and immunotherapy. The developed system presents a safe and effective nanotherapeutic approach for precision breast cancer treatment.
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