Gold-seaurchin based immunomodulator enabling photothermal intervention and αCD16 transfection to boost NK cell adoptive immunotherapy. (1st July 2022)

• Record Type: Journal Article
• Authors: Lin, Xinyi; Li, Feida; Gu, Qing; Wang, Xiaoyan; Zheng, Youshi; Li, Jiong; Guan, Jianhua; Yao, Cuiping; Liu, Xiaolong
• Is Part Of: Acta biomaterialia. Volume 146(2022)
• Page Start: 406
• Page End: 420
• Publication Date: 2022-07-01
• Subjects: Adoptive cell therapy -- Tumor microenvironment remodeling -- Nano immunomodulator -- Photothermal intervention -- Gene transfection; αCD16 CD16 antibody -- αCD16 encoding αCD16 plasmid -- ACT adoptive cell therapy -- ADCC antibody-dependent cellular cytotoxicity -- AuNP Au nanoparticle -- AuNS Au nano-seaurchin -- AuNSP PDMAEM grafted AuNS -- ECM extracellular matrix -- EGFP enhanced green fluorescence protein -- EGFP encoding EGFP plasmid -- GT Gene transfection -- HIF1α hypoxia inducible factor 1 -- HSP70 heat shock protein 70 -- IFN interferon -- IL interleukin -- NIR-II the second near infrared window -- PD PDMAEMA, poly(2-dimethylamino)ethyl methacrylate) -- PTA photothermal agent -- PTT photothermal therapy -- TNF tumor necrosis factor; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1016/j.actbio.2022.04.029
• Languages: English
• ISSNs: 1742-7061

Abstract

Abstract: Despite huge potentials of NK cells in adoptive cell therapy (ACT), formidable physical barriers of the tumor tissue and deficiency of recognizing signals on tumor cells severely prevent NK cell infiltrating, activating and killing performances. Herein, a nano-immunomodulator AuNSP@ αCD16 (CD16 antibody encoding plasmid) is explored to remodel the tumor microenvironment (TME) for improving the antitumor effects of adoptive NK cells. The as-prepared AuNSP, with a seaurchin-like gold core and a cationic polymer shell, exhibited a high gene transfection efficiency and a stable NIR-II photothermal capacity. The AuNSP could trigger mild photothermal intervention to partly destroy tumors and collapse the dense physical barriers, making a permeable TME for NK cell infiltration. What's more, the AuNSP could achieve αCD16 gene transfection to modify tumor surface with CD16 antibody, marking a unique structure on tumor cells for NK cell recognition and then lead to strong NK cell activation by CD16-mediated antibody-dependent cellular cytotoxicity (ADCC). As expected, the designed AuNSP@ αCD16 induced an immune-favorable TME for NK cell performing killing functions against solid tumors, increasing the release of cytolytic granules and proinflammatory cytokines, which ultimately achieved a robustly boosted NK cell-based immunotherapy. Hence, the AuNSP@ αCD16 -mediated TME reconstituting strategy provides a substantial perspective for NK-based ACT on solid tumors. Statement of significance: In adoptive cell therapy (ACT), natural killer (NK) cells exhibit greater off-the-shelf utility and improved safety comparing with T cells, but the efficacy of NK cell therapy is severely compromised by formidable physical barriers of the tumor tissue and deficiency of NK cell recognizing signals on tumor cells. Herein, a nano-immunomodulator AuNSP@ αCD16, with the abilities of inducing mild photothermal intervention and modifying the tumor cell surface with αCD16, is explored to reconstruct an infiltration-favorable and activation-facilitating tumor microenvironment for NK cells to perform killing functions. Such a simple and safe strategy is believed as a very promising candidate for future NK-based ACT. Graphical abstract: Image, graphical abstract