Cell autophagy is a well-known phenomenon in cancer, which limits the efficacy of cancer therapy, especially cancer starvation therapy. Glucose oxidase (GOx), which is considered as an attractive starvation reagent for cancer therapy, can effectively catalyze the conversion of glucose into gluconic acid and hydrogen peroxide (H₂O₂) in the presence of O₂. However, tumor cells adapt to survive by inducing autophagy, limiting the therapy effect. Therefore, anti-cell adaptation via autophagy inhibition could be used as a troubleshooting method to enhance tumor starvation therapy. Herein, we introduce an anti-cell adaptation strategy based on dendritic mesoporous organosilica nanoparticles (DMONs) loaded with GOx and 3-methyladenine (3-MA) (an autophagy inhibition agent) to yield /3-MA. This formulation can inhibit cell adaptative autophagy after starvation therapy. Our in vitro and in vivo results demonstrate that autophagy inhibition enhances the efficacy of starvation therapy, leading to tumor growth suppression. This anti-cell adaptation strategy will provide a new way to enhance the efficacy of starvation cancer therapy.

中文翻译：

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基于葡萄糖氧化酶/3-甲基腺嘌呤负载的树枝状介孔有机硅纳米颗粒的增强型癌症饥饿疗法


细胞自噬是癌症中众所周知的现象，它限制了癌症治疗，尤其是癌症饥饿疗法的疗效。葡萄糖氧化酶(GOx)被认为是癌症治疗中有吸引力的饥饿试剂，在O ₂存在的情况下可以有效催化葡萄糖转化为葡萄糖酸和过氧化氢(H ₂ O ₂ )。然而，肿瘤细胞通过诱导自噬来适应生存，限制了治疗效果。因此，通过自噬抑制的抗细胞适应可以作为增强肿瘤饥饿疗法的故障排除方法。在此，我们介绍了一种基于负载GOx和3-甲基腺嘌呤（3-MA）（一种自噬抑制剂）的树突状介孔有机二氧化硅纳米粒子（DMON）的抗细胞适应策略，以产生/3-MA。该制剂可以抑制饥饿治疗后的细胞适应性自噬。我们的体外 和体内 结果表明，自噬抑制增强了饥饿疗法的功效，从而抑制肿瘤生长。这种抗细胞适应策略将为增强饥饿癌症治疗的疗效提供新途径。