Differential Macrophage Responses to Gold Nanostars and Their Implication for Cancer Immunotherapy

Gold nanostars (AuNSs) are actively explored for a range of theranostic and nanomedicine applications. While their biological applications are widely demonstrated, the fundamental interactions of these anisotropic nanomaterials with innate immune cells and their implication for cancer immunotherapy are less investigated. Specifically, it remains unclear how AuNSs interact with macrophages of different phenotypes and how these interactions influence the behavior of macrophages, especially their phagocytic and cancer modulating activities. Herein, the interactions between AuNSs of different shapes and macrophages of different phenotypes, including the naive M0, pro-inflammatory M1-like, and anti-inflammatory M2-like phenotypes, are systematically interrogated. This study reveals that the morphology of AuNSs significantly impacts their interactions with macrophages. Macrophage viability, oxidative stress response, cytokine release, and phagocytotic ability depend on the macrophage phenotype as well as AuNS shape tip-to-core ratio. The selective response of macrophages toward AuNSs, particularly those of M1-like phenotype, may be potentially leveraged for realizing cancer immunotherapy. Overall, it is anticipated that the findings of this study will further shape the understanding of the interactions between innate immune cells and Au nanomaterials and potentially open new opportunities for cancer therapy.