g(m1)-ganglioside and stearylamine

Although anti-tumor strategies targeting tumor-associated immune cells were being rapidly developed, the preparations were usually limited in targeting efficiency. To overcome this barrier, this study reported a novel sialic acid-octadecylamine (SA-ODA) and monosialotetrahexosylganglioside (GM1) co-modified epirubicin liposomes (5-5-SAGL-EPI), which improved tumor-targeting ability through the active targeting of tumor-associated macrophages (TAMs) by SA-ODA and the long circulation of GM1. Thus, we evaluated 5-5-SAGL-EPI in vitro and in vivo. Analysis of cellular uptake by RAW264.7 cells using flow cytometry and confocal microscopy showed a higher rate of cellular uptake for 5-5-SAGL-EPI than for the common liposomes (CL-EPI). In pharmacokinetic studies using Wistar rats, compared to CL-EPI, 5-5-SAGL-EPI showed a higher circulation time in vivo. Tissue distribution studies in Kunming mice bearing S180 tumors revealed increased distribution of 5-5-SAGL-EPI in tumor tissues compared with liposomes modified with single ligands (SA-ODA [5-SAL-EPI] or GM1 [5-GL-EPI]). In vivo anti-tumor experiments using the S180 tumor-bearing mice revealed a high tumor inhibition rate and low toxicity for 5-5-SAGL-EPI. Moreover, freeze-dried 5-5-SAGL-EPI had good storage stability, and the anti-tumor effect was comparable to that before freeze-drying. Overall, 5-5-SAGL-EPI exhibited excellent anti-tumor effects before and after lyophilization.

Topics: Animals; Cell Line, Tumor; G(M1) Ganglioside; Liposomes; Mice; N-Acetylneuraminic Acid; Rats; Rats, Wistar; Tumor Microenvironment; Tumor-Associated Macrophages

Tritium-labeled neoglycolipids consisting of the oligosaccharide of ganglioside GM1 attached to cholesterol (GM1OSNH-X-CHOL), phosphatidylethanolamine (GM1OS-PE) and stearylamine (GM1OSNHC18) were synthesized and their uptake and metabolism by GM1-deficient rat glioma C6 cells were determined. When the neoglycolipids were added to serum-free culture medium, all three were rapidly taken up by the cells and initially inserted into the plasma membrane based on their resistance to trypsin and their ability to bind cholera toxin. With time, the neoglycolipids underwent internalization as the ratio of cell-associated radioactivity to cell surface toxin binding increased; this process was slow for GM1OSNH-X-CHOL and GM1OS-PE and rapid for GM1OSNHC18. Analysis of lipids extracted from the cells indicated that the neoglycolipids also underwent metabolism to GD1aOS-based analogues. In addition, GM1OSNH-X-CHOL and GM1OSNHC18 were degraded to their GM2OS-based analogues, whereas GM2OS-PE was not detected. In contrast, large amounts of 3H were recovered in the medium from cells treated with GM1OS-PE and the label was associated with material that behaved neither as an oligosaccharide or a neoglycolipid. In the presence of monensin or chloroquine, metabolism of the three neoglycolipids was inhibited. Thus, GM1OS-based neoglycolipids were taken up by the cells, internalized and sorted both to the Golgi apparatus (sialylated to GD1aOS-based analogues) and to lysosomes (hydrolyzed to GM2OS-based analogues). The rate and extent of these processes, however, were strongly influenced by the nature of lipid moiety.

Topics: Amines; Animals; Carbohydrate Sequence; Chloroquine; Cholesterol; G(M1) Ganglioside; Glioma; Molecular Sequence Data; Monensin; Phosphatidylethanolamines; Rats; Tumor Cells, Cultured

Topics: Amines; Aspergillus; Aspergillus oryzae; beta-Galactosidase; Cholesterol; G(M1) Ganglioside; Galactosidases; Galactosylceramides; Liposomes; Phosphatidylcholines; Phospholipids; Psychosine; Substrate Specificity; Sulfoglycosphingolipids