title: Gd(III)-Gold Nanoconjugates Provide Remarkable Cell Labeling for High Field Magnetic Resonance Imaging.
abstract: In vivo cell tracking is vital for understanding migrating cell populations, particularly cancer and immune cells. Magnetic resonance (MR) imaging for long-term tracking of transplanted cells in live organisms requires cells to effectively internalize Gd(III) contrast agents (CAs). Clinical Gd(III)-based CAs require high dosing concentrations and extended incubation times for cellular internalization. To combat this, we have devised a series of Gd(III)-gold nanoconjugates (Gd@AuNPs) with varied chelate structure and nanoparticle-chelate linker length, with the goal of labeling and imaging breast cancer cells. These new Gd@AuNPs demonstrate significantly enhanced labeling compared to previous Gd(III)-gold-DNA nanoconstructs. Variations in Gd(III) loading, surface packing, and cell uptake were observed among four different Gd@AuNP formulations suggesting that linker length and surface charge play an important role in cell labeling. The best performing Gd@AuNPs afforded 23.6 ± 3.6 fmol of Gd(III) per cell at an incubation concentration of 27.5 μM-this efficiency of Gd(III) payload delivery (Gd(III)/cell normalized to dose) exceeds that of previous Gd(III)-Au conjugates and most other Gd(III)-nanoparticle formulations. Further, Gd@AuNPs were well-tolerated in vivo in terms of biodistribution and clearance, and supports future cell tracking applications in whole-animal models.
authors.affiliation: Department of Chemistry, Molecular Biosciences, Neurobiology, Biomedical Engineering, and Radiology, Northwestern University , 2145 Sheridan Road, Evanston, Illinois 60208-3113, United States.
authors.forename: Nikhil
authors.initials: N
authors.lastname: Rammohan
authors.affiliation: Department of Chemistry, Molecular Biosciences, Neurobiology, Biomedical Engineering, and Radiology, Northwestern University , 2145 Sheridan Road, Evanston, Illinois 60208-3113, United States.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Holbrook
authors.affiliation: Department of Chemistry, Molecular Biosciences, Neurobiology, Biomedical Engineering, and Radiology, Northwestern University , 2145 Sheridan Road, Evanston, Illinois 60208-3113, United States.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Rotz
authors.affiliation: Department of Chemistry, Molecular Biosciences, Neurobiology, Biomedical Engineering, and Radiology, Northwestern University , 2145 Sheridan Road, Evanston, Illinois 60208-3113, United States.
authors.forename: Keith W
authors.initials: KW
authors.lastname: MacRenaris
authors.affiliation: Department of Chemistry, Molecular Biosciences, Neurobiology, Biomedical Engineering, and Radiology, Northwestern University , 2145 Sheridan Road, Evanston, Illinois 60208-3113, United States.
authors.forename: Adam T
authors.initials: AT
authors.lastname: Preslar
authors.affiliation: Department of Chemistry, Molecular Biosciences, Neurobiology, Biomedical Engineering, and Radiology, Northwestern University , 2145 Sheridan Road, Evanston, Illinois 60208-3113, United States.
authors.forename: Christiane E
authors.initials: CE
authors.lastname: Carney
authors.affiliation: Department of Chemistry, Molecular Biosciences, Neurobiology, Biomedical Engineering, and Radiology, Northwestern University , 2145 Sheridan Road, Evanston, Illinois 60208-3113, United States.
authors.forename: Viktorie
authors.initials: V
authors.lastname: Reichova
authors.affiliation: Department of Chemistry, Molecular Biosciences, Neurobiology, Biomedical Engineering, and Radiology, Northwestern University , 2145 Sheridan Road, Evanston, Illinois 60208-3113, United States.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Meade
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005682:Gadolinium / Q000737:chemistry*; D006046:Gold / Q000737:chemistry*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D013058:Mass Spectrometry; D051379:Mice; D058726:Nanoconjugates / Q000737:chemistry*
chemical_list: D058726:Nanoconjugates; D006046:Gold; D005682:Gadolinium