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, OCT-polyethylene glycol-stearic acid (OCT-Phe-PEG-A) 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 (Cy7-OCC, Cy7-OCC-OCT), and their physicochemical properties were compared with DOX-loaded micelles (DOX-OCC and DOX-OCC-OCT). All micelles were less than 120 nm with spherical shape and zeta potential of around -30 mV. Enhanced tumor-targeting capacity of OCC-OCT micelles was observed in BALB/c nude mice bearing MCF-7 cancer xenografts as compared with the OCC micelles. Moreover, pharmacodynamic studies demonstrated that DOX-OCC-OCT presented a strongest inhibition of tumor growth and lowest systemic toxicity compared with the DOX solution and DOX-OCC micelles. All the results indicated that OCC-OCT micelles might be a promising tumor-targeting carrier for cancer therapy.
State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.
Aifeng
A
Zou
Yan
Y
Chen
Meirong
M
Huo
Jing
J
Wang
Yong
Y
Zhang
Jianping
J
Zhou
Qiang
Q
Zhang
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000031:analogs & derivatives / Q000737:chemistry* / Q000633:toxicity; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D004337:Drug Carriers; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D015282:Octreotide / Q000031:analogs & derivatives / Q000737:chemistry* / Q000633:toxicity; D061848:Optical Imaging / Q000379:methods; D010316:Particle Size; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008823:Micelles; D004317:Doxorubicin; D048271:Chitosan; D015282:Octreotide