Doxorubicin-conjugated β-NaYF4:Gd3+/Tb3+ 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:Gd³⁺/Tb³⁺ 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:Gd³⁺/Tb³⁺ making them suitable for simultaneous magnetic resonance imaging. In addition, an anticancer drug, doxorubicin (DOX) was conjugated to the amine-functionalized β-NaYF₄:Gd³⁺/Tb³⁺ 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:Gd³⁺/Tb³⁺ 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:Gd³⁺/Tb³⁺ nanorods were studied in tumor microenvironment conditions (pH 6.5) using confocal imaging, which showed an increased uptake of DOX-conjugated β-NaYF₄:Gd³⁺/Tb³⁺ nanorods. Thus, DOX-conjugated β-NaYF₄:Gd³⁺/Tb³⁺ 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.