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: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.

Bifunctional Luminomagnetic Rare-Earth Nanorods for High-Contrast Bioimaging Nanoprobes

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“…Bifunctional nanomaterials that possess desirable properties in a single entity have been the focus of cutting edge science in recent years12345. For instance, nanomaterials with bifunctional properties such as luminescence, magnetism and high contrast bioimaging with magnetic resonance imaging (MRI) contrast capability can be used in a wide range of applications in biological systems such as bioimaging, diagnostic, and therapeutics234678.…”

Luminescent Ions in Advanced Composite Materials for Multifunctional Applications

“…As a result, luminescent nanocomposites should be an option to face the challenge. Doxorubicin (DOX) has been routinely used as a drug model for many proof‐of‐concept anti‐tumor drug delivery systems . Lin's group has done many excellent works along this direction.…”

Self‐Stabilized Hyaluronate Nanogel for Intracellular Codelivery of Doxorubicin and Cisplatin to Osteosarcoma

“…Thus, the drug release efficiency would have such a prominent increase under acidic conditions. Moreover, DOX had also an accelerated release at a lower pH due to its increased hydrophilicity in acid condition 14. This accurate and variable DOX release properties at different pH values make CDDP HANG/DOX accelerate the DOX release in tumor microenvironment, and maintain a low premature leakage in physiological conditions.…”