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

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.