期刊
JOURNAL OF NANOMATERIALS
卷 2016, 期 -, 页码 -出版社
HINDAWI LTD
DOI: 10.1155/2016/1039258
关键词
-
资金
- Mexican National Council of Science and Technology [CONACYT-SEP-CB-2014-01-242443]
- International Atomic Energy Agency [18358]
Lu-177-labeled nanoparticles conjugated to biomolecules have been proposed as a new class of theranostic radiopharmaceuticals. The aim of this research was to synthesize Lu-177-dendrimer(PAMAM-G4)-folate-bombesin with gold nanoparticles (AuNPs) in the dendritic cavity and to evaluate the radiopharmaceutical potential for targeted radiotherapy and the simultaneous detection of folate receptors (FRs) and gastrin-releasing peptide receptors (GRPRs) overexpressed in breast cancer cells. p-SCN-Benzyl-DOTA was conjugated in aqueous-basic medium to the dendrimer. The carboxylate groups of Lys(1) Lys(3) (DOTA)-bombesin and folic acid were activated with HATU and also conjugated to the dendrimer. The conjugate was mixed with 1% HAuCl4 followed by the addition of NaBH 4 and purified by ultrafiltration. Elemental analysis (EDS), particle size distribution (DLS), TEM analysis, UV-Vis, and infrared and fluorescence spectroscopies were performed. The conjugate was radiolabeled using (LuCl3)-Lu-177 or (GaCl3)-Ga-68 and analyzed by radio-HPLC. Studies confirmed the dendrimer functionalization with high radiochemical purity (> 95%). Fluorescence results demonstrated that the presence of AuNPs in the dendritic cavity confers useful photophysical properties to the radiopharmaceutical for optical imaging. Preliminary binding studies in T47D breast cancer cells showed a specific cell uptake (41.15 +/- 2.72%). Lu-177-dendrimer(AuNP)-folate-bombesin may be useful as an optical and nuclear imaging agent for breast tumors overexpressing GRPR and FRs, as well as for targeted radiotherapy.
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