PURPOSE: 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. METHODS: 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. RESULTS: 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. DISCUSSION AND CONCLUSION: 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.
PURPOSE: 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. METHODS: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. RESULTS: 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. DISCUSSION AND CONCLUSION: 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.
Authors: Ivy Ka Man Law; David Miguel Padua; Dimitrios Iliopoulos; Charalabos Pothoulakis Journal: Am J Physiol Gastrointest Liver Physiol Date: 2017-08-03 Impact factor: 4.052
Authors: Philipp Klahn; Verena Fetz; Antje Ritter; Wera Collisi; Bettina Hinkelmann; Tatjana Arnold; Werner Tegge; Katharina Rox; Stephan Hüttel; Kathrin I Mohr; Joachim Wink; Marc Stadler; Josef Wissing; Lothar Jänsch; Mark Brönstrup Journal: Chem Sci Date: 2019-04-15 Impact factor: 9.825
Authors: Rehab A Alshammari; Fadilah S Aleanizy; Amal Aldarwesh; Fulwah Y Alqahtani; Wael A Mahdi; Bushra Alquadeib; Qamraa H Alqahtani; Nazrul Haq; Faiyaz Shakeel; Hosam G Abdelhady; Ibrahim A Alsarra Journal: Pharmaceutics Date: 2022-07-11 Impact factor: 6.525