Sulfatides-containing liposomes as novel nano carriers targeting gliomas

Abstract

Malignant gliomas represent a difficult therapeutic challenge due to the invasive nature of the tumor and limited tumoral delivery of therapeutic agents. In this study, novel nano liposome carriers composed of sulfatides were developed for the glioma targeted delivery. Firstly, sulfatides-containing liposomes (SCLs) were found to interact with glioma cells specifically. The specific interactions between sulfatides and tenascin-c (TN-C), a glioma overexpressed protein, may have an important role. Secondly, the mechanism of intracellular delivery of SCLs was studied. SCLs were found to be effectively internalized in glioma cells by both clathrin-dependent and caveolae/lipids rafts pathways. Thirdly, doxorubicin (DOX) was effectively loaded into the SCLs to form a liposomal drug, SCL-DOX. SCL-DOX could effectively accumulate in the nuclei of glioma cells that resulted in superior in vitro cytotoxicity. In a subcutaneous xenografts animal model, SCL-DOX could effectively inhibit tumor growth and increase the mean life span by 33% compared to control groups. Finally, in an orthotopic tumor xenograft animal model study, SCLs of smaller size were found to effectively bypass the blood brain barrier and accumulate in the brain tumor.