Acidic pH and High-H 2 O 2 Dual Tumor Microenvironment-Responsive Nanocatalytic Graphene Oxide for Cancer Selective Therapy and Recognition

• Published in: ACS applied materials & interfaces 2019-03, Vol.11 (12), p.11157-11166
• Main Authors: Lin, Baoping, Chen, Heting, Liang, Danyang, Lin, Wei, Qi, Xiaoyang, Liu, Hanping, Deng, Xiaoyuan
• Format: Article
• Language: English
• Subjects: Animals; Blood Cells - cytology; Blood Cells - metabolism; Catalase - chemistry; Catalase - metabolism; Catalysis; Cell Survival - drug effects; Dopamine - chemistry; Female; Graphite - chemistry; HeLa Cells; Humans; Hydrogen Peroxide - chemistry; Hydrogen-Ion Concentration; Mice; Mice, Inbred BALB C; Nanoparticles - chemistry; Nanoparticles - metabolism; Nanoparticles - therapeutic use; Nanoparticles - toxicity; Neoplasms - drug therapy; Neoplasms - pathology; Reactive Oxygen Species - metabolism; Transplantation, Heterologous; Tumor Microenvironment
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/acsami.8b22487

It is well known that tumors have an acidic pH microenvironment and contain a high content of hydrogen peroxide (H O ). 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 H O 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 H O , N-GOs exhibit catalase-like activity (scavenge ROS) that splits H O into O and water (H O), 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-H O 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.