Ultra‐Galactocation to Sialic Acid on Tumor Cells with A Penta‐Functional Dendritic Probe for Enhanced Immune‐Killing

Abstract Glycans on tumor cell surface have significant impacts in the immune‐killing process. Here an ultra‐galactocation to sialic acid (Sia) strategy is designed to hugely introduce galactose (Gal) to Sia and on tumor cells in vivo by using a penta‐functional dendritic probe (Den@5F), which efficiently enhances the immune‐killing of tumor cells. The Den@5F contains five different kinds of functional groups, including Gal, Cy5, amino, phenylboronic acid (PBA) and 4‐(4‐(hydroxymethyl)‐2‐methoxy‐5‐nitrophenoxy) butanoate (mNB), which can be conveniently prepared through a two‐step reaction. After injecting into the tumor‐bearing mouse, Den@5F can efficiently block Sia through the specific recognition between PBA and Sia on tumor cells and hugely introduce Gal through the subsequent photo‐crosslinking between mNB and amino groups to multiply conjugate excessive Den@5Fs. The comprehensively blocked Sia can prevent the immune escape, and the hugely introduced Gal can promote the immune stimulation of the immune cells, which lead to an efficient enhancement of the immune‐killing. The proposed strategy provides a significant and promising tool to promote the clinical immunotherapy of tumor.