Paclitaxel-loaded solid lipid nanoparticles modified with Tyr-3-octreotide for enhanced anti-angiogenic and anti-glioma therapy

摘要

Somatostatin receptors (SSTRs) especially subtype 2 (SSTR2) are overexpressed in glioma. By taking advantage of the specific expression of SSTR2 on both glioma neovasculature endothelial cells and glioma cells, we constructed Tyr-3-octreotide (TOC)-modified solid lipid nanoparticles (SLN) loaded with paclitaxel (PTX) to enable tumor neovasculature and tumor cells dual-targeting chemotherapy. In this work, a TOC-polyethylene glycol-lipid (TOC-PEG-lipid) was successfully synthesized and used as a targeting molecule to enhance anticancer efficacy of PTX loaded sterically stabilized lipid nanoparticles. The prepared PTX-loaded SLN modified with TOC (PSM) was characterized by standard methods. In rat C6 glioma cells, PSM improved PTX induced apoptosis. Both tube formation assay and CD31 staining of treated orthotopic glioma tissues confirmed that PSM significantly improved the antiangiogenic ability of PTX in vitro and in vivo, respectively. Radiolabelled PSM achieved a much higher and specific accumulation within the glioma as suggested by the biodistribution and imaging studies. Furthermore, PSM exhibited improved anti-glioma efficacy over unmodified nanoparticles and Taxol in both subcutaneous and orthotopic tumor models. These findings collectively indicate that PSM holds great potential in improving the efficacy of anti-glioma therapy.