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细胞膜包裹的磁性纳米颗粒增强自然杀伤细胞介导的癌症免疫治疗。

Cell membrane-encapsulated magnetic nanoparticles for enhancing natural killer cell-mediated cancer immunotherapy.

机构信息

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China; Institute for Translational Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.

Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, Department of Biomedical Engineering, School of Medicine, Shenzhen University, Shenzhen, China; State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu, China.

出版信息

Nanomedicine. 2021 Feb;32:102333. doi: 10.1016/j.nano.2020.102333. Epub 2020 Nov 12.

Abstract

Natural killer (NK) cells have exhibited therapeutic potential for various malignant tumors. However, the cytotoxic effect of NK cells is relatively weak and less specific compared to other immunotherapy approaches such as chimeric antigen receptor T-Cell (CART) therapy, constituting a great challenge for adoptive immunotherapy. Here, we report cell membrane-encapsulated magnetic nanoparticles for activating NK cells and enhancing anti-tumor effects. Magnetic nanoparticles were coated with silicon dioxide (SiO), and cancer cell membranes were mixed with FeO@SiO to construct cancer cell membrane coated FeO@SiO magnetic nanoparticles (CMNPs). The functionalized nanoparticles bearing cancer-specific antigens on the surface effectively stimulated NK cells by enhancing expression of surface activating receptors and boosting anti-tumor function through the secretion of soluble cytotoxic effectors. To conclude, the biomimetic magnetic nanoparticles offer a versatile and powerful tool to present tumor-specific antigens, priming anti-tumor capability, which is promising to enhance NK cell-based adoptive cancer immunotherapy.

摘要

自然杀伤 (NK) 细胞在各种恶性肿瘤的治疗中显示出了潜力。然而,与嵌合抗原受体 T 细胞 (CART) 疗法等其他免疫疗法相比,NK 细胞的细胞毒性作用相对较弱且特异性较低,这对过继免疫疗法构成了巨大挑战。在这里,我们报告了一种用于激活 NK 细胞和增强抗肿瘤作用的细胞膜包裹的磁性纳米颗粒。磁性纳米颗粒用二氧化硅 (SiO) 进行涂层处理,将癌细胞膜与 FeO@SiO 混合,构建了具有癌细胞膜的 FeO@SiO 磁性纳米颗粒 (CMNPs)。表面带有肿瘤特异性抗原的功能化纳米颗粒通过增强表面激活受体的表达并通过分泌可溶性细胞毒性效应物来增强抗肿瘤功能,从而有效地刺激 NK 细胞。总之,仿生磁性纳米颗粒为呈现肿瘤特异性抗原提供了一种通用且强大的工具,从而增强了抗肿瘤能力,有望增强基于 NK 细胞的过继性癌症免疫疗法。

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