Sialic Acid-Targeting Lectin-Conjugated Oxygen Nanosomes Alleviate Hypoxia and Promote Macrophage Activation in Pancreatic Cancer Cells.

Abstract

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is characterized by severe hypoxia and an immunosuppressive tumor microenvironment, which contribute to poor therapeutic responses. This study developed sialic acid-targeting Lectin-conjugated oxygen nanosomes (Lectin-ONs) to combine targeted oxygen delivery with hypoxia alleviation and macrophage activation.

Methods: SNA- and MALII-conjugated oxygen nanosomes (SNA-ONs and MALII-ONs) were prepared and characterized for physicochemical properties, oxygen-loading and release behavior, stability, cytocompatibility, and cellular binding. Their effects on hypoxia and macrophage activation were evaluated in pancreatic cancer cell models and macrophage-pancreatic cancer cell co-culture using hypoxia-sensitive fluorescence and TNF-α secretion, respectively.

Results: Lectin-ONs exhibited stable physicochemical properties, effective oxygen delivery, and cellular binding to pancreatic cancer cells, while reducing hypoxia-associated fluorescence under oxygen-limited conditions. Treatment with Lectin-ONs also increased TNF-α secretion in macrophage-pancreatic cancer cell co-culture, consistent with macrophage activation.

Conclusion: Lectin-ONs integrate sialic acid-targeted delivery with oxygen-mediated hypoxia alleviation and were associated with increased macrophage TNF-α secretion in vitro. These findings support Lectin-ONs as a potential platform for modulating the hypoxic and immunosuppressive microenvironment of pancreatic cancer, although further mechanistic and in vivo validation is required.