title: Bcl-2-functionalized ultrasmall superparamagnetic iron oxide nanoparticles coated with amphiphilic polymer enhance the labeling efficiency of islets for detection by magnetic resonance imaging.
abstract: Based on their versatile, biocompatible properties, superparamagnetic iron oxide (SPIO) or ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are utilized for detecting and tracing cells or tumors in vivo. Here, we developed an innoxious and concise synthesis approach for a novel B-cell lymphoma (Bcl)-2 monoclonal antibody-functionalized USPIO nanoparticle coated with an amphiphilic polymer (carboxylated polyethylene glycol monooleyl ether [OE-PEG-COOH]). These nanoparticles can be effectively internalized by beta cells and label primary islet cells, at relatively low iron concentration. The biocompatibility and cytotoxicity of these products were investigated by comparison with the commercial USPIO product, FeraSpin(™) S. We also assessed the safe dosage range of the product. Although some cases showed a hypointensity change at the site of transplant, a strong magnetic resonance imaging (MRI) was detectable by a clinical MRI scanner, at field strength of 3.0 Tesla, in vivo, and the iron deposition/attached in islets was confirmed by Prussian blue and immunohistochemistry staining. It is noteworthy that based on our synthesis approach, in future, we could exchange the Bcl-2 with other probes that would be more specific for the targeted cells and that would have better labeling specificity in vivo. The combined results point to the promising potential of the novel Bcl-2-functionalized PEG-USPIO as a molecular imaging agent for in vivo monitoring of islet cells or other cells.
authors.affiliation: Department of Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.forename: Haolei
authors.initials: H
authors.lastname: Cai
authors.forename: Wenjie
authors.initials: W
authors.lastname: Qin
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Chuanxin
authors.initials: C
authors.lastname: Zhai
authors.forename: Biao
authors.initials: B
authors.lastname: Jiang
authors.forename: Yulian
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D007340:Insulinoma; D016381:Islets of Langerhans Transplantation; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010190:Pancreatic Neoplasms; D011092:Polyethylene Glycols / Q000737:chemistry*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D003287:Contrast Media; D058185:Magnetite Nanoparticles; D019253:Proto-Oncogene Proteins c-bcl-2; D011092:Polyethylene Glycols
keywords: MRI; USPIO; beta cells; cell tracing; islet transplantation; nanoparticle functionalization