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Macrophages loaded CpG and GNR-PEI for combination of tumor photothermal therapy and immunotherapy

载GNR-PEI/CpG巨噬细胞用于肿瘤的光热和免疫联合治疗

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Abstract

Nano-therapeutic approach for clinical implementation of tumors remains a longstanding challenge in the medical field. The main challenges are rapid clearance, offtarget effect and the limited role in the treatment of metastatic tumors. Toward this objective, a cell-mediated strategy by transporting photothermal reagents and CpG adjuvant within macrophage vehicles is performed. The photothermal reagents are constructed by conjugating of hyperbranched polyethyleimine (PEI) to golden nanorode (GNR) via S-Au bonds. GNR-PEI/CpG nanocomposites, formed via electrostatic interaction and displayed excellent near-infrared (NIR) photothermal performance, exhibit immense macrophage uptake and negligible cytotoxic effect, which is essential for the fabrication of GNR-PEI/CpG loaded macrophages. GNR-PEI/CpG loaded macrophages demonstrated admirable photothermal response in vitro. Benefited from the functionalization of the binding adhesion between macrophages and 4T1 cells, GNR-PEI/CpG loaded macrophages significantly promoted tumor accumulation in vivo and dramatically enhanced the efficiency of photothermal cancer therapy. Moreover, the immune system is activated after photothermal therapy, which is mainly attributed to the generation of tumor specific antigens and CpG adjuvant in situ. Our findings provide a potential cell-mediated nanoplatform for tumor therapy by combination of near infrared photothermal therapy and immunotherapy.

摘要

纳米药物在肿瘤治疗的临床应用是生物医学领域中长期存在的挑战. 主要问题包括: 体内快速清除、脱靶现象以及对转移瘤治疗 的局限性. 本论文用超支化PEI对金纳米棒进行修饰, 获得了带有正电性的GNR-PEI, 再与负电性的CpG佐剂进行静电复合, 形成GNRPEI/CpG纳米复合物. 为了提高体内适用性和靶向性, 我们进一步构建了载GNR-PEI/CpG的巨噬细胞, 用于肿瘤的光热和免疫联合治疗. 体外研究结果表明, 巨噬细胞具有高效的担载GNR-PEI/CpG的能力, 且载GNR-PEI/CpG巨噬细胞具有很好的光热转换能力. 体内研究结 果进一步预示了该策略在肿瘤治疗领域的巨大潜力.

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Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (51390484, 21474104, 51403205, 51503200 and 51520105004), National program for support of Top-notch young professionals, and Jilin province science and technology development program (20160204032GX, 20180414027GH).

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China

    Jie Chen  (陈杰), Lin Lin  (林琳), Nan Yan  (燕楠), Yingying Hu  (胡莹莹), Huapan Fang  (方华攀), Zhaopei Guo  (郭兆培), Huayu Tian  (田华雨) & Xuesi Chen  (陈学思)

  2. Changchun Golden Transfer Science and Technology Co. Ltd., Changchun, 130022, China

    Pingjie Sun  (孙平杰)

Authors
  1. Jie Chen  (陈杰)
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  2. Lin Lin  (林琳)
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  3. Nan Yan  (燕楠)
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  4. Yingying Hu  (胡莹莹)
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  6. Zhaopei Guo  (郭兆培)
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  8. Huayu Tian  (田华雨)
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  9. Xuesi Chen  (陈学思)
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Corresponding authors

Correspondence to Huayu Tian  (田华雨) or Xuesi Chen  (陈学思).

Additional information

Jie Chen, born in 1982, is currently an associate professor in Changchun Institute of Applied Chemistry, Chinese Academy of Sciences. His research interests are focused on gene delivery and immunotherapy. He has published more than 50 papers in SCI journals and 5 Chinese invention patents.

Lin Lin, born in 1982, is currently an assistant professor in Changchun Institute of Applied Chemistry, Chinese Academy of Sciences. Her research interests are focused on gene carriers design and evaluation. She has published more than 20 papers in SCI journals and 3 Chinese invention patents.

Huayu Tian was born in 1977. Currently, he is a professor in Changchun Institute of Applied Chemistry, Chinese Academy of Sciences. His research interests are focused on polymeric carriers for gene diagnosis and combinational therapy. He published more than 100 papers in SCI journals, such as Progress in Polymer Science, Nano Letters, Biomaterials and Small. He was authorized 15 Chinese invention patents. He was funded by the National Natural Science Funds for excellent Young Scholar and selected for National Program for support of Top-notch Young Professionals.

Xuesi Chen was born in 1959. Currently, he is a professor in Changchun Institute of Applied Chemistry, Chinese Academy of Sciences. His research interests are focused on polymers chemistry on biomedical polymers, drug/gene controlled released carriers designed by biodegradable polymers, bone repair parts and tissue engineering scaffolds from biodegradable polymers. He published more the 500 papers in SCI journals, such as Progress in Polymer Science, Advanced Materials, Advanced Functional Materials, Advanced Drug Delivery Review, and Nano Letters. He was authorized more than 110 Chinese invention patents.

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Chen, J., Lin, L., Yan, N. et al. Macrophages loaded CpG and GNR-PEI for combination of tumor photothermal therapy and immunotherapy. Sci. China Mater. 61, 1484–1494 (2018). https://doi.org/10.1007/s40843-018-9238-6

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  • DOI: https://doi.org/10.1007/s40843-018-9238-6

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