Designing Gold-Seaurchin-Based Nano-Immunomodulator to Remodel Tumor Microenvironment Via Photothermal Intervention and αCD16 Gene Expression for Boosting NK Cell Adoptive Immunotherapy

Abstract

Despite the huge potential of NK cells in adoptive cell therapy (ACT), formidable physical barriers of the tumor tissue and deficient recognizing signals on tumor cells severely prevent NK cell infiltrating, activating and killing performances. Herein, a novel nano-immunomodulator AuNSP@αCD16 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 an excellent gene transfection ability 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 migration and infiltration. What’s more, the AuNSP could achieve αCD16 gene transfection to modify tumor surface with human CD16 antibody, marking a unique structure on tumor cells for NK recognition and then lead to strong NK activation by CD16-mediated antibody-dependent cellular cytotoxicity (ADCC). The AuNSP@αCD16 induces an immune-favorable TME for NK cell performing killing functions against solid tumors, increasing the release of cytolytic granules and proinflammatory cytokines, which ultimately could achieve a robustly boosted NK cell-based immunotherapy. Hence, the designed AuNSP@αCD16-mediated TME reconstituting strategy provides a substantial perspective for NK-based ACT on solid tumors.

Keywords: Adoptive cell therapy, Tumor microenvironment remodeling, Nano immunomodulator, Photothermal intervention, Gene transfection