Lanthanide-Doped Core–Shell–Shell Nanocomposite for Dual Photodynamic Therapy and Luminescence Imaging by a Single X-ray Excitation Source

Abstract

Photodynamic therapy (PDT) could be highly selective and noninvasive, with low side effects as an adjuvant therapy for cancer treatment. Because excitation sources such as UV and visible lights for most of the photosensitizers do not penetrate deeply enough into biological tissues, PDT is useful only when the lesions are located within 10 mm below the skin. In addition, there is no prior example of theranostics capable of both PDT and imaging with a single deep-penetrating X-ray excitation source. Here we report a new theranostic scintillator nanoparticle (ScNP) composite in a core-shell-shell arrangement, that is, NaLuF:Gd(35%),Eu(15%)@NaLuF:Gd(40%)@NaLuF:Gd(35%),Tb(15%), which is capable of being excited by a single X-ray radiation source to allow potentially deep tissue PDT and optical imaging with a low dark cytotoxicity and effective photocytotoxicity. With the X-ray excitation, the ScNPs can emit visible light at 543 nm (from Tb) to stimulate the loaded rose bengal (RB) photosensitizer and cause death of efficient MDA-MB-231 and MCF-7 cancer cells. The ScNPs can also emit light at 614 and 695 nm (from Eu) for luminescence imaging. The middle shell in the core-shell-shell ScNPs is unique to separate the Eu in the core and the Tb in the outer shell to prevent resonance quenching between them and to result in good PDT efficiency. Also, it was demonstrated that although the addition of a mesoporous SiO layer resulted in the transfer of 82.7% fluorescence resonance energy between Tb and RB, the subsequent conversion of the energy from RB to generate O was hampered, although the loaded amount of the RB was almost twice that without the mSiO layer. A unique method to compare the wt % and mol % compositions calculated by using the morphological transmission electron microscope images and the inductively coupled plasma elemental analysis data of the core, core-shell, and core-shell-shell ScNPs is also introduced.

Nd3+ sensitized core-shell-shell nanocomposites loaded with IR806 dye for photothermal therapy and up-conversion luminescence imaging by a single wavelength NIR light irradiation

“…Coating mSiO 2 on the surface of oleate-capped UCNP was prepared according to the previously reported method 60 . Cetyltrimethyl-ammonium chloride (CTAC, 0.2 g) and the previously prepared core-shell-shell UCNPs (5 mg) were dissolved in 25 mL water at 50 °C with stirring overnight.…”

A Cyclic‐RGD Dinuclear TbIII Macrocyclic Complex as a Tumor Integrin‐Selective Luminescent Probe

“…For future studies, in addition to reducing the non‐specific binding, It would be helpful to design Ln III chelates or other substances such as nanocomposites with longer wavelength excitation (e.g. λ ex > 380 nm or preferably in the near infrared region) or X‐ray excitation for more convenient, deep‐penetrating in vivo bioimaging applications.…”

Dynamic Emission Tuning of X‐ray Radioluminescent Crystalline Colloidal Arrays: Coupling the Optical Stop Band with Sequential Förster Resonance Energy Transfers

“…Due to the tissue penetration depths afforded to X‐ray radiation relative to the visible spectrum, imaging techniques that exploit X‐ray sensitive agents have been a focus of growing research interest both as negative and positive contrast agents, while the coupling of diagnostic and therapeutic roles for scintillating probes, generally inorganic systems, which convert X‐ray energy into visible/NIR light have also been recently explored . For example, in the theranostic role, the poor efficiency of 1 O 2 generation by organic photodynamic therapy (PDT) photosensitizers has been mitigated by coupling the photosensitizers with scintillating particles to stimulate the PDT photosensitizers .…”