Chiral Bismuth Molybdate Nanoparticles Recruiting and Activating Group 3 Innate Lymphoid Cells to Suppress Gastric...

Gastric cancer poses a formidable therapeutic challenge due to high heterogeneity and aggressive invasiveness. To address this challenge, we first prepared chiral Bi₂Mo₃O₁₂ nanoparticles (NPs) that exhibited a strong circular dichroism signal of approximately 160 mdeg at 920 nm wavelength. Notably, intraperitoneal injection of L-Bi₂Mo₃O₁₂ NPs achieved complete tumor clearance, as evidenced by extended survival, maintained body weight, and reduced tumor burden. Mechanistically, L-Bi₂Mo₃O₁₂ NPs initially activated PI3K-Akt and NF-κB signaling pathways via the Toll-like receptor 2 (TLR2) in splenic macrophages, thereby increasing interleukin-6 (IL-6) production. Notably, reactive oxygen species (ROS) generated from molybdenum valence change further amplified the NF-κB pathway. Subsequently, IL-6 was transported to the tumor site via the circulation to activate the JAK-STAT signaling pathway in mouse forestomach carcinoma (MFC) cells, leading to the upregulation of C-X-C motif chemokine ligand 16 (CXCL16). This CXCL16 then recruited intestinal-derived group 3 innate lymphoid cells (ILC 3s), which elevated CXCL10 expression. Ultimately, CXCL10 activated T cells and natural killer (NK) cells, thereby mediating tumor elimination. These findings highlight L-Bi₂Mo₃O₁₂ NPs as a promising candidate for tumor immunotherapy.