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

人类自然杀伤细胞用于靶向递送金纳米星和双峰成像定向光热/光动力治疗和免疫治疗

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作者:Bin Liu, Wen Cao, Jin Cheng, Sisi Fan, Shaojun Pan, Lirui Wang, Jiaqi Niu, Yunxiang Pan, Yanlei Liu, Xiyang Sun, Lijun Ma, Jie Song, Jian Ni, Daxiang Cui

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.

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.

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.

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.

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