Manganese@Albumin Nanocomplex and Its Assembled Nanowire Activate TLR4‐Dependent Signaling Cascades of Macrophages

• DOI: 10.1002/adma.202310979
• Publication Date: 2023-11-23T15:41:03Z
• Authors: Shuodan Huang; Yan Gao; Huiying Li; Ruoran Wang; Xiaomei Zhang; Xiaoyu Wang; Di Huang; Linxuan Zhang; Hélder A. Santos; Zhenyu Yin; Bing Xia
• Keywords: Bovine serum albumin

Abstract The immunomodulatory effect of divalent manganese cations (Mn 2+ ), such as activation the cGAS−STING pathway or NLRP3 inflammasomes, positions them adjuvants for cancer immunotherapy. In this study, it is found that trace Mn ions, bound to bovine serum albumin (BSA) form Mn@BSA nanocomplexes, stimulate pro‐inflammatory responses in human‐ murine‐derived macrophages through TLR4‐mediated signaling cascades. Building on this, assembly nanocomplexes obtain nanowire structures enables stronger and longer‐lasting immunostimulation by regulating phagocytosis. Furthermore, their nanowires efficiently activate peritoneal macrophages, reprogramme tumor‐associated inhibit growth melanoma tumors vivo. They also show better biosafety potential clinical applications compared typical TLR4 agonists lipopolysaccharides. Accordingly, findings provide insights into mechanism metalloalbumin complexes TLR macrophage polarization highlight importance nanostructures macrophage‐mediated innate immunity.