Fucoidan‐Modified Au Nanocups With Tumor Targeting Inhibits CD24‐Mediated Immune Escape and Epithelial Mesenchymal Transition Through Precise Controlled Release of Anti‐CD24 Antibodies

Abstract The presence of circulating tumor cells (CTCs) and inadequate immune response limit the therapy effectiveness of tumor metastasis. Epithelial‐mesenchymal transition (EMT), serving as the pivotal initial step in the formation of CTCs, plays a critical role in facilitating tumor metastasis. High expression of CD24 in tumor cells is strongly associated with EMT and immune evasion, but little work has been reported on the inhibitory effect of CD24 blockade on EMT. Here, a nanotherapeutic agent (Au/anti‐CD24@Fu) is fabricated through loading anti‐CD24 antibodies (anti‐CD24) onto Au nanocups, accompanied by surface modification with Fucoidan (Fu). Fu serves as a guide, while Au functions as a controller, jointly facilitating the precise delivery of anti‐CD24 to the tumor site and enabling controlled release. The synergistic collaboration between Fu and anti‐CD24 effectively eliminates the “don't eat me” signal mediated by CD24, thereby augmenting macrophage recognition and phagocytosis. Additionally, it simultaneously obstructs the EMT process facilitated by CD24‐P‐selectin from both ends, consequently impeding the formation of CTCs. Au/anti‐CD24@Fu displays favorable antitumor and anti‐metastasis effect in both 4T1‐bearing mice model and patient‐derived xenografts (PDX) model. This study validates the significance of CD24 blockade in augmenting the antitumor immune response and suppressing the EMT process.