title: Preparation and evaluation of APTES-PEG coated iron oxide nanoparticles conjugated to rhenium-188 labeled rituximab.
abstract: Radioimmuno-conjugated (Rhenium-188 labeled Rituximab), 3-aminopropyltriethoxysilane (APTES)-polyethylene glycol (PEG) coated iron oxide nanoparticles were synthesized and then characterized. Therapeutic effect and targeting efficacy of complex were evaluated in CD20 express B cell lines and tumor bearing Balb/c mice respectively. To reach these purposes, superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized using coprecipitation method and then their surface was treated with APTES for increasing retention time of SPIONs in blood circulation and amine group creation. In the next step, N-hydroxysuccinimide (NHS) ester of polyethylene glycol maleimide (NHS-PEG-Mal) was conjugated to the APTES-treated SPIONs. After radiolabeling of Rituximab antibody with Rhenium-188 (T1/2=16.9h) using synthesized N2S4chelator, it was attached to the APTES-PEG-MAL-SPIONs surface through thiol-maleimide coupling reaction. In vitro evaluation of the188ReN2S4-Rituximab-SPION-complex thus obtained revealed that at 24 and 48h post-treatment effective cancer cell killing had been achieved. Bio-distribution study in tumor bearing mice showed capability of this complex for targeted cancer therapy. Active and passive tumor targeting strategies were applied through incorporated anti-CD20 (Rituximab) antibody and also enhanced permeability and retention (EPR) effect of solid tumors for nanoparticles respectively.
authors.affiliation: Department of Energy Engineering and Physics, Amirkabir University of Technology, 15875-4413 Tehran, Iran.
authors.forename: Bakhtiar
authors.initials: B
authors.lastname: Azadbakht
authors.affiliation: Department of Energy Engineering and Physics, Amirkabir University of Technology, 15875-4413 Tehran, Iran. Electronic address: hafarideh@aut.ac.ir.
authors.forename: Hossein
authors.initials: H
authors.lastname: Afarideh
authors.affiliation: Nuclear Science and Technology Research Institute (NSTRI), Tehran, Iran, 14395-836.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ghannadi-Maragheh
authors.affiliation: Nuclear Science and Technology Research Institute (NSTRI), Tehran, Iran, 14395-836.
authors.forename: Ali
authors.initials: A
authors.lastname: Bahrami-Samani
authors.affiliation: Nuclear Science and Technology Research Institute (NSTRI), Tehran, Iran, 14395-836.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Asgari
mesh_terms: D000818:Animals; D002460:Cell Line; D005290:Ferric Compounds / Q000737:chemistry*; D007553:Isotope Labeling; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011437:Propylamines / Q000737:chemistry*; D011868:Radioisotopes; D012211:Rhenium; D000069283:Rituximab / Q000737:chemistry* / Q000493:pharmacokinetics; D012821:Silanes / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D005290:Ferric Compounds; D011437:Propylamines; D011868:Radioisotopes; D012821:Silanes; C000499:ferric oxide; C000615081:Rhenium-188; D011092:Polyethylene Glycols; D000069283:Rituximab; D012211:Rhenium; C477625:amino-propyl-triethoxysilane
keywords: N(2)S(4) chelator; Rhenium-188; Rituximab; Superparamagnetic iron oxide nanoparticles