Original articles
Peng Liu, Xin Xie, Miao Liu, Shuo Hu, Jinsong Ding, Wenhu Zhou. A smart MnO2-doped graphene oxide nanosheet for enhanced chemo-photodynamic combinatorial therapy via simultaneous oxygenation and glutathione depletion[J]. Acta Pharmaceutica Sinica B, 2021, 11(3): 823-834

A smart MnO2-doped graphene oxide nanosheet for enhanced chemo-photodynamic combinatorial therapy via simultaneous oxygenation and glutathione depletion
Peng Liua, Xin Xieb, Miao Liua, Shuo Huc,d, Jinsong Dinga, Wenhu Zhoua,b,d
a Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, China;
b School of Pharmaceutical Sciences, Gannan Medical University, Ganzhou 341000, China;
c Department of Nuclear Medicine, Xiangya Hospital, Central South University, Changsha 410008, China;
d Key Laboratory of Biological Nanotechnology of National Health Commission, Changsha 410008, China
The combination of chemotherapy and photodynamic therapy provides a promising approach for enhanced tumor eradication by overcoming the limitations of each individual therapeutic modality. However, tumor is pathologically featured with extreme hypoxia together with the adaptable overexpression of anti-oxidants, such as glutathione (GSH), which greatly restricts the therapeutic efficiency. Here, a combinatorial strategy was designed to simultaneously relieve tumor hypoxia by self-oxygenation and reduce intracellular GSH level to sensitize chemo-photodynamic therapy. In our system, a novel multifunctional nanosystem based on MnO2-doped graphene oxide (GO) was developed to co-load cisplatin (CisPt) and a photosensitizer (Ce6). With MnO2 doping, the nanosystem was equipped with intelligent functionalities: (1) catalyzes the decomposition of H2O2 into oxygen to relieve the tumor hypoxia; (2) depletes GSH level in tumor cells, and (3) concomitantly generates Mn2+ to proceed Fenton-like reaction, all of which contribute to the enhanced anti-tumor efficacy. Meanwhile, the surface hyaluronic acid (HA) modification could facilitate the targeted delivery of the nanosystem into tumor cells, thereby resulting in amplified cellular toxicity, as well as tumor growth inhibition in nude mice model. This work sheds a new light on the development of intelligent nanosystems for synergistic combination therapy via regulating tumor microenvironment.
Key words:    Cisplatin    Nanoparticles    Photosensitizer    Tumor microenvironment    Oxygenation    GSH depletion    Nanozyme    Targeting   
Received: 2020-05-12     Revised: 2020-07-19
DOI: 10.1016/j.apsb.2020.07.021
Funds: This work was supported by Innovation-Driven Project of Central South University (No. 20170030010004, China), National Natural Science Foundation of China (No. 21804144, U1903125, China), Project of Hunan Science and Technology (No. 2020JJ8091, China), and Hunan Engineering Research Center for Optimization of Drug Formulation and Early Clinical Evaluation (No. 2015TP2005, China).
Corresponding author: Wenhu Zhou     Email:zhouwenhuyaoji@163.com
Author description:
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Peng Liu
Xin Xie
Miao Liu
Shuo Hu
Jinsong Ding
Wenhu Zhou

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