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Neutrophil-mediated anticancer drug delivery for suppression of postoperative malignant glioma recurrence

Nature Nanotechnology volume 12, pages 692–700 (2017)Cite this article

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Abstract

Cell-mediated drug-delivery systems have received considerable attention for their enhanced therapeutic specificity and efficacy in cancer treatment. Neutrophils (NEs), the most abundant type of immune cells, are known to penetrate inflamed brain tumours. Here we show that NEs carrying liposomes that contain paclitaxel (PTX) can penetrate the brain and suppress the recurrence of glioma in mice whose tumour has been resected surgically. Inflammatory factors released after tumour resection guide the movement of the NEs into the inflamed brain. The highly concentrated inflammatory signals in the brain trigger the release of liposomal PTX from the NEs, which allows delivery of PTX into the remaining invading tumour cells. We show that this NE-mediated delivery of drugs efficiently slows the recurrent growth of tumours, with significantly improved survival rates, but does not completely inhibit the regrowth of tumours.

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Figure 1: Schematic design of NE-mediated anticancer drug delivery for the suppression of postoperative glioma recurrence.
Figure 2: Preparation and characterization of PTX-CL/NEs.
Figure 3: Inflammation-directed sequential delivery.
Figure 4: Pro-inflammatory cytokines are upregulated in the glioma surgical resection model.
Figure 5: PTX-CL/NEs are recruited to the brain and mediate an antitumour effect.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81273468, 81473153), the National Basic Research Program of China (2015CB755500), the State Key Laboratory of Natural Medicines at China Pharmaceutical University (SKLNMZZCX201401) and the 111 Project from the Ministry of Education of China and the State Administration of Foreign Expert Affairs of China (No. 111-2-07). We thank P. Shen, Y. Yang, X. Liu and L. Liu for valuable comments and suggestions.

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  1. State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing, 210009, China

    Jingwei Xue, Zekai Zhao, Lei Zhang, Lingjing Xue, Shiyang Shen, Yajing Wen, Zhuoyuan Wei, Lu Wang, Lingyi Kong, Hongbin Sun, Qineng Ping, Ran Mo & Can Zhang

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  1. Jingwei Xue
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Contributions

J.X. designed and performed the experiments, and analysed the data. Z.Z., L.Z., S.S., Y.W. and Z.W. performed the experiments. L.X. and L.K. characterized the cationic lipid. L.W. synthesized the cationic lipid. H.S. and Q.P. analysed the data of the evaluation of the physiological functions of NEs. R.M. designed the experiments, analysed and interpreted the data, and wrote the manuscript. C.Z. conceived and supervised the project, and analysed and interpreted the data. All the authors discussed the results and reviewed the manuscript.

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Correspondence to Ran Mo or Can Zhang.

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Xue, J., Zhao, Z., Zhang, L. et al. Neutrophil-mediated anticancer drug delivery for suppression of postoperative malignant glioma recurrence. Nature Nanotech 12, 692–700 (2017). https://doi.org/10.1038/nnano.2017.54

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