Enhanced Cancer Starvation Therapy Based on Glucose Oxidase/3-Methyladenine-Loaded Dendritic Mesoporous OrganoSilicon Nanoparticles.

Enhanced Cancer Starvation Therapy Based on Glucose Oxidase/3-Methyladenine-Loaded Dendritic Mesoporous OrganoSilicon Nanoparticles.
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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癌症饥饿治疗。

DOI:
10.3390/biom11091363
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发表时间:
2021-09-14
期刊:
影响因子:
5.5
通讯作者:
Wu Y
Wu Y
中科院分区:
生物学2区
文献类型:
--
作者:
Wu F;Liu Y;Cheng H;Meng Y;Shi J;Chen Y;Wu Y

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细胞自噬是癌症中众所周知的现象,它限制了癌症治疗的效果,特别是癌症饥饿治疗。葡萄糖氧化酶(GOx)在氧气存在下能有效地催化葡萄糖转化为葡萄糖酸和过氧化氢(H2 O2),被认为是一种有吸引力的肿瘤治疗饥饿剂。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用作故障排除方法以增强肿瘤饥饿治疗。在此,我们介绍了一种基于负载GOx和3-甲基腺嘌呤(3-MA)(自噬抑制剂)的树枝状介孔有机硅纳米颗粒(DMON)的抗细胞适应策略,以产生DMON@GOx/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,自噬抑制增强饥饿疗法的功效,导致肿瘤生长抑制。这种抗细胞适应策略将为提高饥饿癌症治疗的疗效提供新的途径。
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 DMON@GOx/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.
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