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

Objective: To construct a novel nanoplatform GNS@CaCO3/Ce6-NK by loading the CaCO3-coated gold nanostars (GNSs) withChlorin e6 molecules (Ce6) into human peripheral blood mononuclear cells (PBMCs)-derived NK cells for tumor targetedtherapy. Methods: GNS@CaCO3/Ce6 nanoparticles were prepared and characterized by TEM and UV-vis. The cell surface markers andcytokines 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) andFCM at different time points. Intracellular ROS generation of GNS@CaCO3/Ce6-NK cells under laser irradiation were examinedby FCM. The distribution of GNS@CaCO3/Ce6-NK in A549 tumor-bearing mice were observed by fluorescence imaging and PAimaging. 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 thecellular uptake process. The as-prepared multifunctional GNS@CaCO3/Ce6-NK cells possessed bimodal functions of fluorescenceimaging and photoacoustic imaging. The as-prepared multifunctional GNS@CaCO3/Ce6-NK cells could actively target tumortissues with the enhanced photothermal/photodynamic therapy and immunotherapy. Conclusions: The GNS@CaCO3/Ce6-NK shows effective tumor-targeting ability and prominent therapeutic efficacy toward lungcancer A549 tumor-bearing mice. Through fully utilizing the features of GNSs and NK cells, this new nanoplatform provides anew synergistic strategy for enhanced photothermal/photodynamic therapy and immunotherapy in the field of anticancerdevelopment in the near future. Cite this article as: Liu B, Cao W, Cheng J, Fan S, Pan S, Wang L, et al.Human natural killer cells for targeting delivery of gold nanostars andbimodal imaging directed photothermal/photodynamic therapy andi m m u n o t h e r a p y . C a n c e r B i o l M e d . 2 0 1 9 ; 1 6 : 7 5 6 - 7 0 . d o i :10.20892/j.issn.2095-3941.2019.0112