In vivo studies of octreotide-modified N-octyl-O, N-carboxymethyl chitosan micelles loaded with doxorubicin for tumor-targeted delivery

Octreotide (OCT) was recently found to have a high binding affinity for the somatostatin receptor expressed on tumor cells. In this study, OCTpolyethylene glycolstearic acid (OCTPhePEGA) was used as a targeting molecule for N-octyl-O, N-carboxymethyl chitosan (OCC) micelles loaded with doxorubicin (DOX). For in vivo fluorescence imaging, the fluorescent probe Cyanine 7 (Cy7) was successfully loaded into OCC micelles with or without OCT modification (Cy7OCC, Cy7OCCOCT), and their physicochemical properties were compared with DOX-loaded micelles (DOXOCC and DOXOCCOCT). All micelles were less than 120?nm with spherical shape and zeta potential of around -30?mV. Enhanced tumor-targeting capacity of OCCOCT micelles was observed in BALB/c nude mice bearing MCF-7 cancer xenografts as compared with the OCC micelles. Moreover, pharmacodynamic studies demonstrated that DOXOCCOCT presented a strongest inhibition of tumor growth and lowest systemic toxicity compared with the DOX solution and DOXOCC micelles. All the results indicated that OCCOCT micelles might be a promising tumor-targeting carrier for cancer therapy. (c) 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:126135, 2013