Glycan-targeted gold nanorod nanoplatform for photothermal immunotherapy of pancreatic cancer

Despite the clinical successes of adaptive immune checkpoint blockade, sialic acid-mediated interactions associated with the Siglec-10/CD24 “don’t eat me” pathway can contribute to impaired macrophage-mediated clearance in pancreatic cancer. Here, we report a dual-targeting gold nanorod platform (Man-AuNR-SNA) designed to combine glycan-mediated targeting with photothermal therapy. The nanoplatform targets CD206-expressing M2-like macrophages via mannose and recognizes sialylated pancreatic cancer cells via SNA lectin. Dual functionalization enhanced macrophage–cancer cell interactions compared with single-target controls, supporting complementary contributions of mannose- and SNA-mediated targeting. NIR-triggered photothermal treatment induced apoptotic cancer cell death and, in a PANC-1 xenograft model, achieved 70.9% tumor growth inhibition, comparable to that observed with gemcitabine. Treatment was also associated with an increased CD86/CD206 ratio and changes in macrophage-associated gene expression consistent with a more pro-inflammatory phenotype. These findings support the integration of glycan-mediated macrophage–cancer cell targeting with photothermal therapy as a potential strategy for pancreatic cancer treatment.