Acidic pH and High-H2O2 Dual Tumor Microenvironment-Responsive Nanocatalytic Graphene Oxide for Cancer Selective Therapy and Recognition,ACS Applied Materials & Interfaces

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Acidic pH and High-H2O2 Dual Tumor Microenvironment-Responsive Nanocatalytic Graphene Oxide for Cancer Selective Therapy and Recognition
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2019-03-14 00:00:00 , DOI: 10.1021/acsami.8b22487
Baoping Lin ₁ , Heting Chen ₁ , Danyang Liang ₁ , Wei Lin ₁ , Xiaoyang Qi ₁ , Hanping Liu ₁ , Xiaoyuan Deng ₁

Affiliation

It is well known that tumors have an acidic pH microenvironment and contain a high content of hydrogen peroxide (H₂O₂). These features of the tumor microenvironment may provide physiochemical conditions that are suitable for selective tumor therapy and recognition. Here, for the first time, we demonstrate that a type of graphene oxide nanoparticle (N-GO) can exhibit peroxidase-like activities (i.e., can increase the levels of reactive oxygen species (ROS)) under acidic conditions and catalyze the conversion of H₂O₂ to ROS-hydroxyl radicals (HO^·) in the acidic microenvironment in Hela tumors. The concentrated and highly toxic HO^· can then trigger necrosis of tumor cells. In the microenvironment of normal tissues, which has a neutral pH and low levels of H₂O₂, N-GOs exhibit catalase-like activity (scavenge ROS) that splits H₂O₂ into O₂ and water (H₂O), leaving normal cells unharmed. In the recognition of tumors, an inherent redox characteristic of dopamine is that it oxidizes to form dopamine–quinine under neutral (pH 7.4) conditions, quenching the fluorescence of N-GOs; however, this characteristic has no effect on the fluorescence of N-GOs in an acidic (pH 6.0) medium. This pH-controlled response provides an active targeting strategy for the diagnostic recognition of tumor cells. Our current work demonstrates that nanocatalytic N-GOs in an acidic and high-H₂O₂ tumor microenvironment can provide novel benefits that can reduce drug resistance, minimize side effects on normal tissues, improve antitumor efficacy, and offer good biocompatibility for tumor selective therapeutics and specific recognition.

中文翻译：

酸性pH和高H ₂ O ₂双重肿瘤微环境响应纳米催化氧化石墨烯用于癌症的选择性治疗和识别。

众所周知，肿瘤具有酸性的pH微环境并且含有高含量的过氧化氢（H ₂ O ₂）。肿瘤微环境的这些特征可以提供适合于选择性肿瘤治疗和识别的理化条件。在这里，我们首次证明一种类型的氧化石墨烯纳米颗粒（N-GO）在酸性条件下可以表现出类似过氧化物酶的活性（即可以增加活性氧（ROS）的水平），并催化过氧化氢的转化。在Hela肿瘤的酸性微环境中，H ₂ O ₂为ROS-羟基自由基（HO ^·）。浓缩且剧毒的HO ^·然后会引发肿瘤细胞坏死。在具有中性pH值和低水平H ₂ O ₂的正常组织的微环境中，N-GOs表现出过氧化氢酶样活性（清除ROS），可将H ₂ O ₂分解为O ₂和水（H _2）O），使正常细胞不受伤害。在识别肿瘤时，多巴胺的固有氧化还原特性是在中性（pH 7.4）条件下会氧化形成多巴胺-奎宁，从而淬灭N-GOs的荧光。但是，该特性对酸性（pH 6.0）介质中N-GO的荧光没有影响。pH值控制的响应为肿瘤细胞的诊断识别提供了一种主动的靶向策略。我们当前的工作表明，酸性和高H ₂ O ₂肿瘤微环境中的纳米催化N-GO可以提供新颖的益处，可以降低耐药性，最小化对正常组织的副作用，提高抗肿瘤功效，并为肿瘤选择性治疗提供良好的生物相容性和具体的认可。

更新日期：2019-03-14

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