A novel lanreotide-modified micelle system targets paclitaxel to the tumors with overexpression of somatostatin receptors
Many tumor cells specifically overexpress somatostatin receptors, in particular, subtype 2 (SSTR2). Lanreotide, a somatostatin analog with high affinity for SSTR2, can be exploited as a ligand for tumor targeted therapy. In this study, lanreotide was first used to functionalize poly(ethyleneglycol)-poly (ε-caprolactone)(PEG-b-PCL), and the active targeting micelles with paclitaxel (Lanreotide-PM-PTX) or fluorescent agent were developed and characterized with various analytical methods. Two cell lines (NCI-H446 and MCF-7) with different expression level of SSTR2 were selected as cell models. Lanreotide-PM-PTX was spherical in shape with a hydrodynamic diameter of 43.15±0.38nm, high drug loading density (87.1±2.8％) and slow drug release rate. As observed by flow cytometry, confocal microscopy and cytotoxicity studies, lanreotide modified PEG-PCL micelles demonstrated more specific uptake and cytotoxicity in SSTR2-positive tumor cells in vitro over the passive targeting micelles mostly via a receptor-mediated mechanism. The active targeting micelles were found by the near-infrared fluorescence (NIRF) imaging and confocal microscopy to achieve higher accumulation in tumor tissue and tumor cells in vivo, as well as slow elimination in mice. Furthermore, treatment withLanreotide-PM-PTX resulted in superior antitumor efficacy, enhanced tumor cell apoptosis and less body weight loss in SSTR2-overexpressing tumor model in athymic nude mice, as compared with the control groups. In conclusion, lanreotide can serve as an effective homing peptide, and the lanreotide-modified PEG-PCL micelles hold considerable promise in the treatment of SSTR2-overexpressing solid tumors.
Lanreotide Somatostatin receptors Paclitaxel Active targeting micelles Cellular uptake Distribution in tumor Antitumor efficacy
Nan Zheng Jinming Gao Qiang Zhang Wenbin Dai Wenwen Du Haoran Zhang Liandi Lei Hua Zhang Xueqing Wang Jiancheng Wang Xuan Zhang
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking Univ Harold C. Simmons Comprehensive Cancer Center, Department of Pharmacology,UT Southwestern Medical Ce
国内会议
烟台
英文
1-20
1900-01-01（万方平台首次上网日期，不代表论文的发表时间）