title: A magnetofluorescent nanoparticle for ex-vivo cell labeling by covalently linking the drugs protamine and Feraheme.
abstract: We synthesized a nanoparticle (NP) for ex-vivo cell labeling and MRI tracking by covalently coupling the C-terminus of a rhodamine-labeled protamine (ProRho) to Feraheme (FH) in order to yield the nanoparticle denoted ProRho-FH. Since protamine can adsorb to certain charged surfaces, we confirmed a covalent interaction between ProRho and FH by heparin affinity chromatography. ProRho-FH lacks a net charge (zeta potential approximately 0) due to the combination of negative FH and positive ProRho charges. ProRho-FH was readily internalized by U87 cells and mouse mesenchymal stem cells as determined by FACS and MR relaxometry. Finally, some 4,000 stem cells were implanted in a mouse brain and imaged by MRI. Due to its lack of net surface charge, ProRho-FH relies on the internalizing properties of the surface guanidinium groups present in the arginine-rich protamine to induce NP uptake. ProRho-FH is a unique cell-labeling agent due to its synthesis using two approved drugs, magnetofluorescence, site-specific covalent attachment chemistry, and lack of surface charge.
authors.affiliation: Center for Translational Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02129, USA.
authors.forename: Suelin
authors.initials: S
authors.lastname: Chen
authors.forename: David
authors.initials: D
authors.lastname: Alcantara
authors.forename: Lee
authors.initials: L
authors.lastname: Josephson
mesh_terms: D000818:Animals; D058948:Cell Tracking / Q000379:methods*; D003287:Contrast Media; D006397:Hematinics / Q000008:administration & dosage / Q000737:chemistry; D006494:Heparin Antagonists / Q000008:administration & dosage / Q000737:chemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D051379:Mice; D008856:Microscopy, Fluorescence / Q000379:methods; D053769:Nanocapsules / Q000737:chemistry*; D011479:Protamines / Q000008:administration & dosage* / Q000737:chemistry; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*
chemical_list: D003287:Contrast Media; D006397:Hematinics; D006494:Heparin Antagonists; D058185:Magnetite Nanoparticles; D053769:Nanocapsules; D011479:Protamines