ABSTRACT
Octreotide (Oct) is a potential ligand due to its high affinity to somatostatin receptors (SSTRs), especially subtype 2 (SSTR2), as many tumor cells specifically overexpress SSTR2. In this study, we conjugated Oct to the PEG end of DSPE-PEG and prepared a novel doxorubicin (DOX)-loaded and Oct-modified sterically stabilized liposomes (Oct-SSL-DOX), in order to facilitate intracellular delivery of chemotherapeutic agent to the related tumor cells through active targeting and finally improve its antitumor activity. Three cells were proved to be different in expression level of SSTR2 and were used as model or control. It was demonstrated by fluorescence spectrophotometry, confocal laser scanning microscopy and flow cytometry that active sterically stabilized liposomes (SSL) increased intracellular delivery of DOX in SSTR2-positive cells, through a mechanism of receptor-mediated endocytosis. Compared to SSL, Oct modification on SSL exhibited little effect on the physicochemical properties of SSL. However, it reduced the circulation time of loaded-DOX to some extent in rats, increased cytotoxicity in SSTR2-positive tumor cells, enhanced drug accumulation in tumor tissue and improved anticancer efficacy in SSTR2-overexpressing tumor model. The correlation was found among intracellular uptake, cytotoxicity, drug distribution in tumor and pharmacodynamics of Oct-SSL-DOX, but not the pharmacokinetics based on plasma drug concentration. In summary, octreotide-modified SSL might be a promising system for the treatment of SSTR2-overexpressing cancers.