Theranostics 2020; 10(3):1281-1295. doi:10.7150/thno.40291

Research Paper

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

Weijie Ma1*, Daoming Zhu2*, Jinghua Li1*, Xi Chen1, Wei Xie2, Xiang Jiang1, Long Wu1, Ganggang Wang1, Yusha Xiao1, Zhisu Liu1, Fubing Wang4, Andrew Li5, Dan Shao3,6, Wenfei Dong3✉, Wei Liu2✉, Yufeng Yuan1✉

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.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
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 http://www.thno.org/v10p1281.htm

File import instruction

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.