Coating biomimetic nanoparticles with chimeric antigen receptor T cell-membrane provides high specificity for hepatocellular carcinoma photothermal therapy treatment

Weijie Ma^1*, Daoming Zhu^2*, Jinghua Li^1*, Xi Chen¹, Wei Xie², Xiang Jiang¹, Long Wu¹, Ganggang Wang¹, Yusha Xiao¹, Zhisu Liu¹, Fubing Wang⁴, Andrew Li⁵, Dan Shao^3,6, Wenfei Dong^3✉, Wei Liu^2✉, Yufeng Yuan^1✉

1. Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
2. Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan, 430072, China.
3. Key Laboratory of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, Jiangsu 215163, China.
4. Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
5. Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.
6. Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA.
*These authors contributed equally to this work.

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Citation:
Ma W, Zhu D, Li J, Chen X, Xie W, Jiang X, Wu L, Wang G, Xiao Y, Liu Z, Wang F, Li A, Shao D, Dong W, Liu W, Yuan Y. Coating biomimetic nanoparticles with chimeric antigen receptor T cell-membrane provides high specificity for hepatocellular carcinoma photothermal therapy treatment. Theranostics 2020; 10(3):1281-1295. doi:10.7150/thno.40291. Available from https://www.thno.org/v10p1281.htm

Abstract

Rationale: Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies in the world. Apart from traditional surgical resection, radiotherapy, and chemotherapy, more recent techniques such as nano-photothermal therapy and biotherapy are gradually being adopted for the treatment of HCC. This project intends to combine the advantages of nanoscale drug delivery systems with the targeting ability of CAR-T cells.

Method: Based on cell membrane-coated nanoparticles and cell membrane-targeting modifications, a novel nanomaterial was prepared by coating CAR-T cell membranes specifically recognizing GPC3⁺ HCC cells onto mesoporous silica containing IR780 nanoparticles. Subsequently, the physical properties were characterized, and the in vitro and in vivo targeting abilities of this nanoparticle were verified.

Results: CAR-T cells were constructed which could recognize GPC3 expressed on the cell surface of HCC cells. Then the isolated CAR-T cell membrane was successfully coated on the IR780 loaded mesoporous silica materials, as verified by transmission electron microscopy. The superior targeting ability of CAR-T cell membrane coated nanoparticles compared to IR780 loaded mesoporous silica nanoparticles was verified, both in vitro and in vivo.

Conclusion: This new nanomaterial exhibits photothermal antitumor abilities along with enhanced targeting abilities, suggesting a promising strategy for the treatment of HCC.

Keywords: Nanoparticles, chimeric antigen receptor T cell, cell membrane coating technique, photothermal therapy, hepatocellular carcinoma.