Journal of Drug Targeting 2014-06-01

Octreotide-conjugated PAMAM for targeted delivery to somatostatin receptors over-expressed tumor cells.

Jianqing Peng, Xiaole Qi, Yi Chen, Ning Ma, Ziwei Zhang, Jiaxu Xing, Xuehua Zhu, Zhengrong Li, Zhenghong Wu

文献索引：J. Drug Target. 22(5) , 428-38, (2014)

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摘要

An octreotide-conjugated polyamidoamine (PAMAM) dendrimer was synthesized and employed as nanocarriers of methotrexate (MTX), for targeting to the somatostatin receptors over-expressed tumor cells.PAMAM-PEG-octreotide (PPO) and PAMAM-PEG (PPG) were synthesized and characterized. The cellular uptake of fluorescein isothiocyanate (FITC)-labeled PPO (PPO-FITC) and PPG (PPG-FITC) were investigated. The cytotoxicity of MTX and MTX nanoparticles were conducted in the MCF-7 cells. Besides, the pharmacokinetics studies on MTX nanoparticles were carried out in rats.The structure of PPO was verified by NMR detection and the diameter was 11.05 ± 1.80 nm, with the amount of MTX encapsulated by PPO was 30 (molecule/molecule). MTX nanoparticles possessed significantly higher cytotoxicity against MCF-7 cells compared with free MTX, especially the PPO/MTX nanoparticles. Correspondingly, the PPO-FITC carrier had higher cellular uptake efficiency compared to PPG-FITC. In addition, pharmacokinetics studies showed that PPO/MTX nanoparticles increased mean residence time and bioavailability of MTX distinctly.With further cellular uptake test of FITC-labeled carriers, the enhanced cytotoxicity of PPO/MTX nanoparticles was reasonable to ascribe to the specific receptor-mediated endocytosis induced by octreotide. The present study suggests that this PAMAM-PEG-octreotide nanocarrier opens a new path for treating cancer with higher efficacy.