title: Small multifunctional nanoclusters (nanoroses) for targeted cellular imaging and therapy.
abstract: The ability of 20-50 nm nanoparticles to target and modulate the biology of specific types of cells will enable major advancements in cellular imaging and therapy in cancer and atherosclerosis. A key challenge is to load an extremely high degree of targeting, imaging, and therapeutic functionality into small, yet stable particles. Herein we report approximately 30 nm stable uniformly sized near-infrared (NIR) active, superparamagnetic nanoclusters formed by kinetically controlled self-assembly of gold-coated iron oxide nanoparticles. The controlled assembly of nanocomposite particles into clusters with small primary particle spacings produces collective responses of the electrons that shift the absorbance into the NIR region. The nanoclusters of approximately 70 iron oxide primary particles with thin gold coatings display intense NIR (700-850 nm) absorbance with a cross section of approximately 10(-14) m(2). Because of the thin gold shells with an average thickness of only 2 nm, the r(2) spin-spin magnetic relaxivity is 219 mM(-1) s(-1), an order of magnitude larger than observed for typical iron oxide particles with thicker gold shells. Despite only 12% by weight polymeric stabilizer, the particle size and NIR absorbance change very little in deionized water over 8 months. High uptake of the nanoclusters by macrophages is facilitated by the dextran coating, producing intense NIR contrast in dark field and hyperspectral microscopy, both in cell culture and an in vivo rabbit model of atherosclerosis. Small nanoclusters with optical, magnetic, and therapeutic functionality, designed by assembly of nanoparticle building blocks, offer broad opportunities for targeted cellular imaging, therapy, and combined imaging and therapy.
authors.affiliation: Department of Chemical Engineering, University of Texas at Austin, Austin, Texas 78712, USA.
authors.forename: Li Leo
authors.initials: LL
authors.lastname: Ma
authors.forename: Marc D
authors.initials: MD
authors.lastname: Feldman
authors.forename: Jasmine M
authors.initials: JM
authors.lastname: Tam
authors.forename: Amit S
authors.initials: AS
authors.lastname: Paranjape
authors.forename: Kiran K
authors.initials: KK
authors.lastname: Cheruku
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Larson
authors.forename: Justina O
authors.initials: JO
authors.lastname: Tam
authors.forename: Davis R
authors.initials: DR
authors.lastname: Ingram
authors.forename: Vidia
authors.initials: V
authors.lastname: Paramita
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Villard
authors.forename: James T
authors.initials: JT
authors.lastname: Jenkins
authors.forename: Tianyi
authors.initials: T
authors.lastname: Wang
authors.forename: Geoffrey D
authors.initials: GD
authors.lastname: Clarke
authors.forename: Reto
authors.initials: R
authors.lastname: Asmis
authors.forename: Konstantin
authors.initials: K
authors.lastname: Sokolov
authors.forename: Bysani
authors.initials: B
authors.lastname: Chandrasekar
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Milner
authors.forename: Keith P
authors.initials: KP
authors.lastname: Johnston
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D001692:Biological Transport; D002460:Cell Line; D005290:Ferric Compounds / Q000737:chemistry* / Q000378:metabolism*; D006046:Gold / Q000737:chemistry*; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D008280:Magnetics; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011817:Rabbits; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D013499:Surface Properties
chemical_list: D005290:Ferric Compounds; C000499:ferric oxide; D006046:Gold