title: Doxorubicin-conjugated β-NaYF4:Gd(3+)/Tb(3+) multifunctional, phosphor nanorods: a multi-modal, luminescent, magnetic probe for simultaneous optical and magnetic resonance imaging and an excellent pH-triggered anti-cancer drug delivery nanovehicle.
abstract: Herein, we report the fabrication of a multifunctional nanoprobe based on highly monodispersed, optically and magnetically active, biocompatible, PEI-functionalized, highly crystalline β-NaYF4:Gd(3+)/Tb(3+) nanorods as an excellent multi-modal optical/magnetic imaging tool and a pH-triggered intracellular drug delivery nanovehicle. The static and dynamic photoluminescence spectroscopy showed the presence of sharp emission peaks, with long lifetimes (∼3.5 milliseconds), suitable for optical imaging. The static magnetic susceptibility measurements at room temperature showed a strong paramagnetic signal (χ∼ 3.8 × 10(-5) emu g(-1) Oe(-1)). The nuclear magnetic resonance (NMR) measurements showed fair T1 relaxivity (r1 = 1.14 s(-1) mM(-1)) and magnetic resonance imaging gave enhanced T1-weighted MRI images with increased concentrations of β-NaYF4:Gd(3+)/Tb(3+) making them suitable for simultaneous magnetic resonance imaging. In addition, an anticancer drug, doxorubicin (DOX) was conjugated to the amine-functionalized β-NaYF4:Gd(3+)/Tb(3+) nanorods via pH-sensitive hydrazone bond linkages enabling them as a pH-triggered, site-specific drug delivery nanovehicle for DOX release inside tumor cells. A comparison between in vitro DOX release studies undertaken in normal physiological (pH 7.4) and acidic (pH 5.0) environments showed an enhanced DOX dissociation (∼80%) at pH 5.0. The multifunctional material was also applied as an optical probe to confirm the conjugation of DOX and to monitor DOX release via a fluorescence resonance energy transfer (FRET) mechanism. The DOX-conjugated β-NaYF4:Gd(3+)/Tb(3+) nanorods exhibited a cytotoxic effect on MCF-7 breast cancer cells and their uptake by MCF-7 cells was demonstrated using confocal laser scanning microscopy and flow cytometry. The comparative cellular uptakes of free DOX and DOX-conjugated β-NaYF4:Gd(3+)/Tb(3+) nanorods were studied in tumor microenvironment conditions (pH 6.5) using confocal imaging, which showed an increased uptake of DOX-conjugated β-NaYF4:Gd(3+)/Tb(3+) nanorods. Thus, DOX-conjugated β-NaYF4:Gd(3+)/Tb(3+) nanorods combining pH-triggered drug delivery, efficient luminescence and paramagnetic properties are promising for a potential multifunctional platform for cancer therapy, biodetection, and optical and magnetic resonance imaging.
authors.affiliation: Physical & Materials Chemistry Division, CSIR-National Chemical Laboratory, Pune 411 008, India. p.poddar@ncl.res.in.
authors.forename: Preeti
authors.initials: P
authors.lastname: Padhye
authors.forename: Aftab
authors.initials: A
authors.lastname: Alam
authors.forename: Suvankar
authors.initials: S
authors.lastname: Ghorai
authors.forename: Samit
authors.initials: S
authors.lastname: Chattopadhyay
authors.forename: Pankaj
authors.initials: P
authors.lastname: Poddar
mesh_terms: D000818:Animals; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000494:pharmacology; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D005459:Fluorides / Q000737:chemistry / Q000494:pharmacology; D005682:Gadolinium / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008163:Luminescent Measurements / Q000379:methods*; D061986:MCF-7 Cells; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D041681:NIH 3T3 Cells; D061848:Optical Imaging / Q000379:methods*; D013725:Terbium / Q000737:chemistry / Q000494:pharmacology; D015019:Yttrium / Q000737:chemistry / Q000494:pharmacology
chemical_list: D003692:Delayed-Action Preparations; C525362:sodium yttriumtetrafluoride; D013725:Terbium; D015019:Yttrium; D004317:Doxorubicin; D005682:Gadolinium; D005459:Fluorides