Original Article
Pegylated carbon nitride nanosheets for enhanced reactive oxygen species generation and photodynamic therapy under hypoxic conditions

https://doi.org/10.1016/j.nano.2020.102167Get rights and content

Abstract

The application of photodynamic therapy (PDT) is of ever-increasing importance in the treatment of malignant tumors; however, there are several major constraints that make it impossible to achieve optimal therapeutic effects. Our objective is to develop a novel photosensitizing drug for skin cancer. In the experiment, we fabricated four-arm-poly ethylene glycol modified amino-rich graphite phase carbon nitride nanosheets (AGCN-PEG), which have good stability in physiological solution and show selective accumulation in tumor cells. Under hypoxic conditions, the AGCN-PEG induced PDT can effectively inhibit growth on A431 human epidermoid carcinoma cells in vivo and in vitro. What's more, after being combined with TMPyP4, the therapeutic effect of AGCN-PEG was greatly improved.

Graphical Abstract

In this article, we fabricated four-arm-poly ethylene glycol (4Arm-PEG) modified amino-rich graphite phase carbon nitride nanosheets (AGCN-PEG). Under hypoxic conditions, the AGCN-PEG induced PDT can effectively inhibit growth on A431 human epidermoid carcinoma cells in vivo and in vitro. What's more, after being combined with TMPyP4, the therapeutic effect of AGCN-PEG was greatly improved.

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Section snippets

Methods

We provided a detailed description of materials and methods in the Supplementary Materials.

Results

The morphology of PEG modified amino-rich g-C3N4 nanosheets (AGCN-PEG) was observed by atomic force microscopy (AFM). A layer of PEG coronas surrounding g-C3N4 nanosheets can be observed in Figure 1, B. Particularly, through the height–width profile, the width of the bright spot in the middle is 40-50 nm, the same size as the AGCN-NS measured before (Figure 1, C). Fourier transform infrared spectroscopy (FTIR) is applied to determine the chemical bonds and functional groups of materials. In

Discussion

In this experiment, the principle and function of chemical reaction between four-arm polyethylene glycol and AGCN-NS are shown in Figure 1, A. Under ambient conditions, the carboxyl group of polyethylene glycol does not react with amino-group. In order to react with the amino groups of the AGCN-NS, the carboxyl group of the 4Arm-PEG-COOH has to be activated as an NHS ester, 4Arm-PEG-NHS. The NHS terminal of 4Arm-PEG-NHS is highly active and easy to react with amino groups to form amide bonds.

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    Acknowledgments: This study was supported by National Key R&D Program of China (2019YFA0110600) and National Natural Science Foundation of China (81970986, 81771125). Bulk g-C3N4 was obtained from College of Chemistry, Sichuan University.

    Notes: The authors declare no competing financial interest.

    1

    Qian Huang and Yang Chen contributed equally to this work.

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