Gold-seaurchin based immunomodulator enabling photothermal intervention and aCD16 transfection to boost NK cell adoptive immunotherapy

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@alpha CD16 (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 alpha CD16 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@alpha CD16 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@alpha CD16-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@alpha CD16, with the abilities of inducing mild photothermal intervention and modifying the tumor cell surface with alpha CD16, 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. (C) 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Automated summary

This study explores a nano-immunomodulator, AuNSP@alpha CD16, to improve the antitumor effects of adoptive NK cells by remodeling the tumor microenvironment. The AuNSP can trigger mild photothermal intervention to partially destroy tumors and collapse physical barriers, allowing infiltration of NK cells. It can also modify tumor surface with CD16 antibody, leading to strong NK cell activation. The designed AuNSP@alpha CD16 induces an immune-favorable tumor microenvironment, enhancing the killing functions of NK cells against solid tumors.