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Original Article | Open Access

Human natural killer cells for targeting delivery of gold nanostars and bimodal imaging directed photothermal/photodynamic therapy and immunotherapy

Bin Liu1,2, Wen Cao3, Jin Cheng1,2, Sisi Fan1,2, Shaojun Pan4, Lirui Wang1,2, Jiaqi Niu1,2, Yunxiang Pan1,2, Yanlei Liu1,2, Xiyang Sun5, Lijun Ma5, Jie Song1,2, Jian Ni1,2, Daxiang Cui1,2,5( )
Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China
National Center for Translational Medicine, Collaborative Innovational Center for System Biology, Shanghai Jiao Tong University, Shanghai 200240, China
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, China
School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China
Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 1111 Xian Xia Road, Shanghai 200336, China
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Abstract

Objective

To construct a novel nanoplatform GNS@CaCO3/Ce6-NK by loading the CaCO3-coated gold nanostars (GNSs) with Chlorin e6 molecules (Ce6) into human peripheral blood mononuclear cells (PBMCs)-derived NK cells for tumor targeted therapy.

Methods

GNS@CaCO3/Ce6 nanoparticles were prepared and characterized by TEM and UV-vis. The cell surface markers and cytokines secretion of NK cells before and after loading the GNS@CaCO3/Ce6 nanoparticles were detected by Flow Cytometry (FCM) and ELISA. Effects of the GNS@CaCO3/Ce6-NK cells on A549 cancer cells was determined by FCM and CCK-8. Intracellular fluorescent signals of GNS@CaCO3/Ce6-NK cells were detected via Confocal laser scanning microscopic (CLSM) and FCM at different time points. Intracellular ROS generation of GNS@CaCO3/Ce6-NK cells under laser irradiation were examined by FCM. The distribution of GNS@CaCO3/Ce6-NK in A549 tumor-bearing mice were observed by fluorescence imaging and PA imaging. The combination therapy of GNS@CaCO3/Ce6-NK under laser irradiation were investigated on tumor-bearing mice.

Results

The coated CaCO3 shell on the surface of GNSs exhibited prominent delivery and protection effect of Ce6 during the cellular uptake process. The as-prepared multifunctional GNS@CaCO3/Ce6-NK cells possessed bimodal functions of fluorescence imaging and photoacoustic imaging. The as-prepared multifunctional GNS@CaCO3/Ce6-NK cells could actively target tumor tissues with the enhanced photothermal/photodynamic therapy and immunotherapy.

Conclusions

The GNS@CaCO3/Ce6-NK shows effective tumor-targeting ability and prominent therapeutic efficacy toward lung cancer A549 tumor-bearing mice. Through fully utilizing the features of GNSs and NK cells, this new nanoplatform provides a new synergistic strategy for enhanced photothermal/photodynamic therapy and immunotherapy in the field of anticancer development in the near future.

Keywords

Gold nanostarsnatural killer cellsphotothermal therapyphotodynamic therapyimmunotherapy

Electronic Supplementary Material

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Cancer Biology & Medicine
Volume 16 Issue 4,
November 2019
Pages 756-770
DOI: 10.20892/j.issn.2095-3941.2019.0112
Cite this article:
Liu B, Cao W, Cheng J, et al. Human natural killer cells for targeting delivery of gold nanostars and bimodal imaging directed photothermal/photodynamic therapy and immunotherapy. Cancer Biology & Medicine, 2019, 16(4): 756-770. https://doi.org/10.20892/j.issn.2095-3941.2019.0112

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Received: 31 March 2019
Accepted: 24 June 2019
Published: 01 November 2019
© 2019 by Cancer Biology & Medicine
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