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Multifunctional nanoreactors-integrated microneedles for cascade reaction-enhanced cancer therapy
Journal of Controlled Release ( IF 10.8 ) Pub Date : 2021-10-02 , DOI: 10.1016/j.jconrel.2021.09.041
Yixian Zhou 1 , Boyi Niu 1 , Yiting Zhao 1 , Jintao Fu 1 , Ting Wen 1 , Kaixin Liao 1 , Guilan Quan 2 , Xin Pan 1 , Chuanbin Wu 3
Affiliation  

Starvation therapy based on glucose oxidase (GOx) has attracted considerable attention in tumor treatment. However, several shortcomings severely hinder its further applications, including limited therapeutic efficacy, poor enzyme stability, and potential side effects. Herein, a strategy of cascade reaction-enhanced combined therapy based on the oxygen-evolving multifunctional nanoreactors is proposed for tumor therapy. The GOx and catalase (CAT) are immobilized in metal-organic frameworks by biomimetic mineralization to improve their stability via spatial confinement. The GOx can consume glucose, reduce ATP levels, and down-regulate the expression of heat shock proteins, which consequently sensitize tumor cells to indocyanine green-based photothermal therapy. Furthermore, the hydrogen peroxide generated by GOx as well as overexpressed in tumor can be decomposed by CAT and continuously generate oxygen, which further enhance the efficacy of oxygen-dependent starvation therapy and photodynamic therapy. The nanoreactors are directly delivered to the superficial tumor by microneedles, achieving efficient tumor accumulation and dramatically strengthened antitumor efficacy without obvious side effects, which provides a valuable paradigm for the application of cascade reaction-based combined therapy.



中文翻译:

用于级联反应增强癌症治疗的多功能纳米反应器集成微针

基于葡萄糖氧化酶(GOx)的饥饿疗法在肿瘤治疗中引起了相当大的关注。然而,一些缺点严重阻碍了其进一步应用,包括治疗效果有限、酶稳定性差和潜在的副作用。在此,提出了一种基于析氧多功能纳米反应器的级联反应增强联合治疗策略用于肿瘤治疗。GOx 和过氧化氢酶 (CAT) 通过仿生矿化固定在金属有机框架中,以通过空间限制提高其稳定性。GOx 可以消耗葡萄糖,降低 ATP 水平,并下调热休克蛋白的表达,从而使肿瘤细胞对基于吲哚菁绿的光热疗法敏感。此外,GOx产生的过氧化氢以及在肿瘤中过表达的过氧化氢可以被CAT分解并持续产生氧气,进一步提高了氧依赖饥饿疗法和光动力疗法的疗效。纳米反应器通过微针直接递送至浅表肿瘤,实现了高效的肿瘤积累,并显着增强了抗肿瘤功效,且无明显副作用,为基于级联反应的联合治疗应用提供了有价值的范例。

更新日期:2021-10-09
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