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, NaLuF₄:Gd­(35%),Eu­(15%)@NaLuF₄:Gd­(40%)@NaLuF₄: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 Tb³⁺) 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 Eu³⁺) for luminescence imaging. The middle shell in the core−shell−shell ScNPs is unique to separate the Eu³⁺ in the core and the Tb³⁺ 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 SiO₂ layer resulted in the transfer of 82.7% fluorescence resonance energy between Tb³⁺ and RB, the subsequent conversion of the energy from RB to generate ¹O₂ was hampered, although the loaded amount of the RB was almost twice that without the mSiO₂ 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