Development of Liposomal Nanoconstructs Targeting P-selectin (CD62P)-expressing Cells by Using A Sulfated Derivative of Sialic Acid
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NMSO3, a sulfated derivative of sialic acid, is a specific inhibitor for P-selectin (CD62P)-mediated cell adhesion. We attempted to apply liposomes modified with NMSO3 for selective targeting of activated platelets.
The binding of fluorescently labeled NMSO3-containing liposomes (NMSO3-liposomes) to CHO cells expressing P-selectin (CHO-P cells) and activated platelets were examined. The distribution of NMSO3-liposomes incorporated into the cells was observed by fluorescence microscopy.
The binding assay revealed that NMSO3-liposomes specifically bound to immobilized P-selectin and CHO-P cells in a dose-dependent manner. The binding of NMSO3-liposomes to CHO-P cells was much stronger than that to the parental CHO-K1 cells. Fluorescence microscopic observation showed that NMSO3-liposomes were incorporated into CHO-P cells after the binding and distributed throughout the cytoplasm of the cell. NMSO3-liposomes bound more strongly to thrombin-activated platelets than to resting platelets, as assessed by flow cytometry.
These results suggest that NMSO3-liposomes can be applied for selective drug delivery to activated platelets.
KEY WORDSactivated platelet drug delivery liposome P-selectin sulfated sialyl lipid
Phosphate buffered saline
Sialyl Lewis X
Acknowledgments and Disclosure
We are grateful to Dr. Masaaki Kurihara (Kurihara Clinic, Tokyo, Japan) for his helpful discussion of the study. We also would like to thank Mr. Y. Hirakouchi and Mr. H. Maruyama (Hoshi University School of Pharmacy and Pharmaceutical Sciences) for their technical assistance. This work was supported in part by the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by the Open Research Center Project.
The authors have no potential conflicts of interest to disclose.
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