title: In vitro cellular accumulation of gadolinium incorporated into chitosan nanoparticles designed for neutron-capture therapy of cancer.
abstract: The accumulation of gadolinium loaded as gadopentetic acid (Gd-DTPA) in chitosan nanoparticles (Gd-nanoCPs), which were designed for gadolinium neutron-capture therapy (Gd-NCT) for cancer, was evaluated in vitro in cultured cells. Using L929 fibroblast cells, the Gd accumulation for 12 h at 37 degrees C was investigated at Gd concentrations lower than 40 ppm. The accumulation leveled above 20 ppm and reached 18.0+/-2.7 (mean+/-S.D.) microg Gd/10(6) cells at 40 ppm. Furthermore, the corresponding accumulations in B16F10 melanoma cells and SCC-VII squamous cell carcinoma, which were used in the previous Gd-NCT trials in vivo, were 27.1+/-2.9 and 59.8+/-9.8 microg Gd/10(6) cells, respectively, hence explaining the superior growth-suppression in the in vivo trials using SCC-VII cells. The accumulation of Gd-nanoCPs in these cells was 100-200 times higher in comparison to dimeglumine gadopentetate aqueous solution (Magnevist), a magnetic resonance imaging contrast agent. The endocytic uptake of Gd-nanoCPs, strongly holding Gd-DTPA, was suggested from transmission electron microscopy and comparative studies at 4 degrees C and with the solution system. These findings indicated that Gd-nanoCPs had a high affinity to the cells, probably contributing to the long retention of Gd in tumor tissue and leading to the significant suppression of tumor growth in the in vivo studies that were previously reported.
authors.affiliation: Faculty of Pharmaceutical Sciences and High Technology Research Center, Kobe Gakuin University, Arise 518, Ikawadani-cho, Nishi-ku, Kobe 651-2180, Japan.
authors.forename: Futoshi
authors.initials: F
authors.lastname: Shikata
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tokumitsu
authors.forename: Hideki
authors.initials: H
authors.lastname: Ichikawa
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Fukumori
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000493:pharmacokinetics; D002686:Chitin / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D048271:Chitosan; D005682:Gadolinium / Q000493:pharmacokinetics*; D019786:Gadolinium DTPA / Q000493:pharmacokinetics; D007739:L Cells / Q000378:metabolism / Q000648:ultrastructure; D008546:Melanoma, Experimental / Q000378:metabolism; D051379:Mice; D036103:Nanotechnology / Q000379:methods*; D009369:Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D017247:Neutron Capture Therapy / Q000379:methods*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D002686:Chitin; D048271:Chitosan; D005682:Gadolinium; D019786:Gadolinium DTPA