title: Design and synthesis of polymer-functionalized NIR fluorescent dyes--magnetic nanoparticles for bioimaging.
abstract: The fluorescent probes having complete spectral separation between absorption and emission spectra (large Stokes shift) are highly useful for solar concentrators and bioimaging. In bioimaging application, NIR fluorescent dyes have a greater advantage in tissue penetration depth compared to visible-emitting organic dyes or inorganic quantum dots. Here we report the design, synthesis, and characterization of an amphiphilic polymer, poly(isobutylene-alt-maleic anhyride)-functionalized near-infrared (NIR) IR-820 dye and its conjugates with iron oxide (Fe3O4) magnetic nanoparticles (MNPs) for optical and magnetic resonance (MR) imaging. Our results demonstrate that the Stokes shift of unmodified dye can be tuned (from ~106 to 208 nm) by the functionalization of the dye with polymer and MNPs. The fabrication of bimodal probes involves (i) the synthesis of NIR fluorescent dye (IR-820 cyanine) functionalized with ethylenediamine linker in high yield, >90%, (ii) polymer conjugation to the functionalized NIR fluorescent dye, and (iii) grafting the polymer-conjugated dyes on iron oxide MNPs. The resulting uniform, small-sized (ca. 6 nm) NIR fluorescent dye-magnetic hybrid nanoparticles (NPs) exhibit a wider emissive range (800-1000 nm) and minimal cytotoxicity. Our preliminary studies demonstrate the potential utility of these NPs in bioimaging by means of direct labeling of cancerous HeLa cells via NIR fluorescence microscopy and good negative contrast enhancement in T2-weighted MR imaging of a murine model.
authors.affiliation: Institute of Materials Research and Engineering, Agency for Science, Technology and Research, 3 Research Link, Singapore 117602.
authors.forename: Swee Kuan
authors.initials: SK
authors.lastname: Yen
authors.forename: Dominik
authors.initials: D
authors.lastname: Jańczewski
authors.forename: Jeeva Lavanya
authors.initials: JL
authors.lastname: Lakshmi
authors.forename: Surani Bin
authors.initials: SB
authors.lastname: Dolmanan
authors.forename: Sudhiranjan
authors.initials: S
authors.lastname: Tripathy
authors.forename: Vincent H B
authors.initials: VH
authors.lastname: Ho
authors.forename: Vimalan
authors.initials: V
authors.lastname: Vijayaragavan
authors.forename: Anushya
authors.initials: A
authors.lastname: Hariharan
authors.forename: Parasuraman
authors.initials: P
authors.lastname: Padmanabhan
authors.forename: Kishore K
authors.initials: KK
authors.lastname: Bhakoo
authors.forename: Thankiah
authors.initials: T
authors.lastname: Sudhaharan
authors.forename: Sohail
authors.initials: S
authors.lastname: Ahmed
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Subramanian
authors.initials: S
authors.lastname: Tamil Selvan
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D004396:Coloring Agents / Q000737:chemistry; D003287:Contrast Media / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D007208:Indocyanine Green / Q000031:analogs & derivatives* / Q000737:chemistry; D008280:Magnetics; D051379:Mice; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods; D011108:Polymers / Q000737:chemistry; D013053:Spectrophotometry; D013056:Spectrophotometry, Ultraviolet; D019265:Spectroscopy, Near-Infrared
chemical_list: D001672:Biocompatible Materials; D004396:Coloring Agents; D003287:Contrast Media; D005456:Fluorescent Dyes; C541053:IR 820; D011108:Polymers; D007208:Indocyanine Green