| Title | A Novel Lanreotide-Encoded Micelle System Targets Paclitaxel to the Tumors with Overexpression of Somatostatin Receptors |
| Authors | Zheng, Nan Dai, Wenbing Du, Wenwen Zhang, Haoran Lei, Liandi Zhang, Hua Wang, Xueqing Wang, Jiancheng Zhang, Xuan Gao, Jinming Zhang, Qiang |
| Affiliation | Peking Univ, Sch Pharmaceut Sci, Dept Pharmaceut, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China. Univ Texas SW Med Ctr Dallas, Harold C Simmons Comprehens Canc Ctr, Dept Pharmacol, Dallas, TX 75390 USA. Peking Univ, Sch Pharmaceut Sci, Dept Pharmaceut, State Key Lab Nat & Biomimet Drugs, 38 Xueyuan Rd, Beijing 100191, Peoples R China. |
| Keywords | lanreotide somatostatin receptors paclitaxel active targeting micelles receptor-mediated cellular uptake distribution in tumor antitumor efficacy toxicity BLOCK-COPOLYMER MICELLES DRUG-DELIVERY POLYMERIC MICELLES IN-VIVO PHASE-I CELLULAR UPTAKE OVARIAN-CANCER NANOPARTICLES THERAPY FLUORESCENCE |
| Issue Date | 2012 |
| Publisher | molecular pharmaceutics |
| Citation | MOLECULAR PHARMACEUTICS.2012,9,(5),1175-1188. |
| Abstract | Many tumor cells specifically overexpress somatostatin receptors, in particular, subtype 2 (SSTR2). Lanreotide, a somatostatin analogue with high affinity for SSTR2, can be exploited as a ligand for tumor targeted therapy. In this study, lanreotide was first conjugated to poly(ethylene glycol)-b-poly(epsilon-caprolactone) (PEG-b-PCL) copolymer, and the active targeting micelles with paclitaxel (lanreotide-PM-PTX) or fluorescent agent were constructed and characterized with various analytical methods. Lanreotide-PM-PTX micelles were spherical in shape with hydrodynamic diameter of 43.2 +/- 0.4 nm, high drug encapsulation (87.1 +/- 2.8%) and slow drug release rate. Two cancer cell lines (human lung cancer H446 and human breast cancer MCF-7 cells) with different expression levels of SSTR2 were used in this study. As observed by flow cytometry, confocal microscopy and cytotoxicity studies, lanreotide-encoded PEG-b-PCL micelles demonstrated more specific cell uptake and cytotoxicity in SSTR2-positive tumor cells via a receptor-mediated mechanism over the passive targeting micelles. The active targeting micelles showed higher accumulation in tumor tissue and tumor cells in tumor-bearing mice in vivo by near-infrared fluorescence (NIRF) imaging, high-performance liquid chromatography and confocal microscopy, respectively. Furthermore, treatment with lanreotide-PM-PTX micelles resulted in stronger tumor inhibition, increased life span and enhanced tumor cell apoptosis in SSTR2-overexpressing tumor model in athymic nude mice. The in vivo efficacy test with both H446 and MCF-7 tumor models further demonstrated the involvement of receptor-mediated interaction. Finally, the active targeting micelles exhibited less body weight loss, lower hemolysis and lower myelosuppression, as compared with the control groups. In conclusion, lanreotide can serve as an effective homing peptide, and the lanreotide-modified PEG-b-PCL micelles hold considerable promise in the treatment of SSTR2-overexpressing solid tumors. |
| URI | http://hdl.handle.net/20.500.11897/156622 |
| ISSN | 1543-8384 |
| DOI | 10.1021/mp200464x |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 药学院 天然药物与仿生药物国家重点实验室 |
