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.
To perform photothermal therapy (PTT) and luminescence imaging by a single wavelength NIR light irradiation, we have designed and prepared a novel nanocomposite incorporating the IR806 photothermal sensitizers (PTS) into the core-shell-shell NaYF4:Yb,Er@ NaYF4:Yb@NaYF4:Yb,Nd up-conversion nanoparticles (UCNPs). Irradiation with the 793 nm near-infrared (NIR) laser, the Nd3+ ions in the UCNPs were sensitized to up-convert energy via Yb3+ to the Er3+ ions to emit visible light at 540 nm and 654 nm, as well as to down-convert energy to the Yb3+ ions to emit NIR light at 980 nm. For luminescence imaging, the 793 nm NIR radiation is more suitable to use for deeper-tissue penetration and to reduce overheating problem due to water absorption as compared to 980 nm radiation. Additionally, the same 793 nm NIR radiation could also excite the IR806 dye for effective PTT. Surface modifications of the UCNPs with mesoporous silica (mSiO2) and polyallylamine (PAH) allow stable loading of IR806 dye and further derivatization with polyethylene glycol-folic acid (PEG-FA) for tumor targeting. Preliminary in vitro studies demonstrated that the final UCNP@mSiO2/IR806@PAH-PEG-FA nanocomposites (UCNC-FAs) could be uptaken by the MDA-MB-231 cancer cells and were “dark” viable, and when irradiated with the 793 nm laser, the MDA-MB-231 cell viability was effectively reduced. This indicated that the UCNC-FAs nanocomposites could be potentially useful for targeted photothermal therapy and up-conversion luminescence imaging by a single wavelength NIR light irradiation.
Nanocomposite NaYF4:Nd,Yb@Yb@Yb,Er@Y with Nd3+ in the core and Er3+ in the shell to shorten the emitter (Er3+)–photosensitizer distance to achieve better Förster resonance energy transfer (FRET) for better-performing photo-nanotheranostic materials.
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