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

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.

SUBMITTER: Liu B

PROVIDER: S-EPMC6936231 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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

Liu Bin B Cao Wen W Cheng Jin J Fan Sisi S Pan Shaojun S Wang Lirui L Niu Jiaqi J Pan Yunxiang Y Liu Yanlei Y Sun Xiyang X Ma Lijun L Song Jie J Ni Jian J Cui Daxiang D

Cancer biology & medicine 20191101 4

<h4>Objective</h4>To construct a novel nanoplatform GNS@CaCO<sub>3</sub>/Ce6-NK by loading the CaCO<sub>3</sub>-coated gold nanostars (GNSs) with Chlorin e6 molecules (Ce6) into human peripheral blood mononuclear cells (PBMCs)-derived NK cells for tumor targeted therapy.<h4>Methods</h4>GNS@CaCO<sub>3</sub>/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@CaCO<sub>3</sub>/Ce6 nanopart ...[more]

PMID: 31908893

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Project description:Efficient plasmonic photothermal therapies (PPTTs) using non-harmful pulse laser irradiation at the near-infrared (NIR) are a highly sought goal in nanomedicine. These therapies rely on the use of plasmonic nanostructures to kill cancer cells while minimizing the applied laser power density. Cancer cells have an unsettled capacity to uptake, retain, release, and re-uptake gold nanoparticles, thus offering enormous versatility for research. In this work, we have studied such cell capabilities for nanoparticle trafficking and its impact on the effect of photothermal treatments. As our model system, we chose uveal (eye) melanoma cells, since laser-assisted eye surgery is routinely used to treat glaucoma and cataracts, or vision correction in refractive surgery. As nanostructure, we selected gold nanostars (Au NSs) due to their high photothermal efficiency at the near-infrared (NIR) region of the electromagnetic spectrum. We first investigated the photothermal effect on the basis of the dilution of Au NSs induced by cell division. Using this approach, we obtained high PPTT efficiency after several cell division cycles at an initial low Au NS concentration (pM regime). Subsequently, we evaluated the photothermal effect on account of cell division upon mixing Au NS-loaded and non-loaded cells. Upon such mixing, we observed trafficking of Au NSs between loaded and non-loaded cells, thus achieving effective PPTT after several division cycles under low irradiation conditions (below the maximum permissible exposure threshold of skin). Our study reveals the ability of uveal melanoma cells to release and re-uptake Au NSs that maintain their plasmonic photothermal properties throughout several cell division cycles and re-uptake. This approach may be readily extrapolated to real tissue and even to treat in situ the eye tumor itself. We believe that our method can potentially be used as co-therapy to disperse plasmonic gold nanostructures across affected tissues, thus increasing the effectiveness of classic PPTT.

Dataset Information

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

Publications

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

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