Engineering the Bio‐Nanoscale Interface of Gold Nanocomposites for Cancer Immunotherapy

Abstract

Gold nanocomposites have evolved from passive delivery vehicles into versatile immunomodulators for cancer therapy. However, their clinical utility remains constrained by biological instability and potential toxicity. This review elucidates strategies to overcome these biological barriers through precise engineering of the bio‐nanoscale interface. In the context of solid tumor therapy, we examine how mild photothermal therapy mechanically remodels the tumor stroma, reducing interstitial fluid pressure and triggering immunogenic cell death to sensitize immunosuppressive tumors. Beyond thermal ablation, the review highlights the intrinsic immunostimulatory properties of gold cores, discussing how chiral topologies activate innate immunity and how nanozyme activities regulate the hypoxic tumor microenvironment. Furthermore, we evaluate structural engineering strategies, such as spherical nucleic acids and virus‐mimicking assemblies, for their ability to ensure robust antigen presentation. To address safety concerns regarding long‐term retention, the discussion extends to stimuli‐responsive assembly strategies, which enable the degradation of accumulation competent structures into renal clearable ultrasmall clusters. Finally, we discuss critical barriers to clinical translation, including manufacturing consistency, protein corona heterogeneity, and long‐term biosafety.