iNGR-Modified Liposomes for Tumor Vascular Targeting and Tumor Tissue Penetrating Delivery in the Treatment of Glioblastoma.

The tumor vascular barrier and tumor stroma barrier become the two main obstacles in the in vivo delivery of nanomedicines. In this study, to overcome the two barriers, we used iNGR, a tumor-penetrating peptide, to modify the liposomes to increase their accumulation and penetration in tumor tissues. First, iNGR-modified sterically stabilized liposomes (iNGR-SSL) were prepared, which showed vesicle sizes of about 100 nm and narrow size distribution. The uptake of iNGR-SSL by U87MG cells and HUVECs were significantly more than that of unmodified liposome. The in vivo imaging study demonstrated that iNGR modification remarkably increased the accumulation of the liposome in orthotopic tumor tissues of animal model. The immunofluorescence staining analysis proved that iNGR-SSL could penetrate through tumor blood vessels and into the deep tumor tissues. The cytotoxicity of iNGR-modified doxorubicin-loaded liposomes (iNGR-SSL/DOX) on U87MG and HUVECs cells in vitro was significantly enhanced than that of unmodified doxorubicin-loaded liposomes (SSL/DOX). The iNGR-SSL/DOX also showed comparatively (p < 0.05) stronger cytotoxicity on tumor than SSL/DOX, which should be resulted from the increased tumor accumulation and penetration mediated by iNGR. This study proved that iNGR peptide modification might be an effective method to enhance the tumor penetrating ability of liposomes in tumor tissue and their antitumor effect.