Promoting Oxidative Stress in Cancer Starvation Therapy by Site-Specific Startup of Hyaluronic Acid-Enveloped Dual-Catalytic Nanoreactors,ACS Applied Materials & Interfaces

当前位置： X-MOL 学术 › ACS Appl. Mater. Interfaces › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Promoting Oxidative Stress in Cancer Starvation Therapy by Site-Specific Startup of Hyaluronic Acid-Enveloped Dual-Catalytic Nanoreactors
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2019-05-06 00:00:00 , DOI: 10.1021/acsami.9b06034
Zhigang Yao ₁ , Benhua Zhang ₁ , Tingxizi Liang ₁ , Jie Ding _{1,

2} , Qianhao Min ₁ , Jun-Jie Zhu ₁

Affiliation

Cutting off the glucose supply by glucose oxidase (GOx) has been regarded as an emerging strategy in cancer starvation therapy. However, the standalone GOx delivery suffered suboptimal potency for tumor elimination and potential risks of damaging vasculatures and normal organs during transportation. To enhance therapeutic efficacy and tumor specificity, a site-specific activated dual-catalytic nanoreactor was herein constructed by embedding GOx and ferrocene in hyaluronic acid (HA)-enveloped dendritic mesoporous silica nanoparticles to promote intratumoral oxidative stress in cancer starvation. In this nanoreactor, the encapsulated GOx served as the primary catalyst that accelerated oxidation of glucose and generation of H₂O₂, while the covalently linked ferrocene worked as the secondary catalyst for converting the upstream H₂O₂ to more toxic hydroxyl radicals (^•OH) via a classic Fenton reaction. The outmost HA shell not only offered a shielding layer for preventing blood glucose from oxidation during nanoreactor transportation, thus minimizing the probable oxidative damage to normal tissues, but also imparted the nanoreactor with targeting ability for facilitating its internalization into CD44-overexpressing tumor cells. After the nanoreactor was endocytosed by target cells, the HA shell underwent hyaluronidase-triggered degradation in lysosomes and switched on the cascade catalytic reaction mediated by GOx and ferrocene. The resulting glucose exhaustion and ^•OH accumulation would effectively kill cancer cells and suppress tumor growth via combination of starvation and oxidative stress enhancement. Both in vitro and in vivo results indicated the significantly amplified therapeutic effects of this synergistic therapeutic strategy based on the dual-catalytic nanoreactor. Our study provides a new avenue for engineering therapeutic nanoreactors that take effect in a tumor-specific and orchestrated fashion for cancer starvation therapy.

中文翻译：

通过透明质酸包裹的双催化纳米反应器的特定位置启动来促进癌症饥饿疗法中的氧化应激

通过葡萄糖氧化酶（GOx）切断葡萄糖供应已被认为是癌症饥饿疗法中的新兴策略。但是，独立的GOx递送在消除肿瘤方面没有达到最佳效果，并且在运输过程中可能损害血管和正常器官。为了增强治疗功效和肿瘤特异性，本文通过将GOx和二茂铁嵌入透明质酸（HA）包裹的树状中孔二氧化硅纳米粒子中嵌入以促进癌症饥饿中的肿瘤内氧化应激来构建位点特异性活化的双催化纳米反应器。在这种纳米反应器中，封装的GOx充当主要催化剂，可加速葡萄糖的氧化和H ₂ O _2的产生，而共价连接的二茂铁则作为辅助催化剂，通过经典的Fenton反应将上游的H ₂ O ₂转化为毒性更大的羟基（^• OH）。HA外壳的最外层不仅提供了一个屏蔽层，以防止血糖在纳米反应器运输过程中被氧化，从而将对正常组织的可能的氧化损伤降至最低，而且赋予纳米反应器以靶向能力，以促进其内在化入CD44过表达的肿瘤细胞。纳米反应器被靶细胞内吞后，HA壳在溶酶体中经历了透明质酸酶触发的降解，并启动了由GOx和二茂铁介导的级联催化反应。造成的葡萄糖消耗和^•OH积累将通过饥饿和氧化应激增强相结合，有效杀死癌细胞并抑制肿瘤生长。体外和体内结果均表明基于双催化纳米反应器的这种协同治疗策略的治疗效果显着增强。我们的研究为工程化治疗纳米反应器提供了新途径，该反应器以肿瘤特异性和精心策划的方式在癌症饥饿治疗中发挥作用。

更新日期：2019-05-06

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南