Enhancing Förster Resonance Energy Transfer (FRET) Efficiency of Titania–Lanthanide Hybrid Upconversion Nanomaterials by Shortening the Donor–Acceptor Distance

Abstract

Several robust titania (TiO2) coated core/multishell trivalent lanthanide (Ln) upconversion nanoparticles (UCNPs) hybrid architecture designs have been reported for use in photodynamic therapy (PDT) against cancer, utilizing the near-infrared (NIR) excited energy down-shifting and up-conversion chain of Nd3+ (λ793-808 nm) → Yb3+ (λ980 nm) → Tm3+(λ475 nm) → TiO2 to produce reactive oxygen species (ROS) for deep tissue-penetrating oxidative cytotoxicity, e.g., NaLnF4:Yb,Tm (Ln = Y, Gd). Herein, we demonstrate that by doping the Tm3+ emitter ions in the outer shell and the Nd3+ sensitizer ions in the core, the newly designed NaYF4:Nd,Yb@Yb@Yb,Tm@TiO2 hybrid UCNPs exert more ROS production than the reference NaYF4:Yb,Tm@Yb@Nd,Yb@ TiO2 with the Tm3+ ions in the core and the Nd3+ ions in the outer shell, upon 793 nm laser irradiation, primarily due to the shortening of the Tm3+-TiO2 distance of the former with greater Förster resonance energy transfer (FRET) efficiency. After coating with polyallylamine hydrochloride (PAH)/polyethylene glycol folate (PEG-FA), the resulting NaYF4:Nd,Yb@Yb@Yb,Tm@TiO2-PAH-PEG-FA hybrid nanocomposites could be internalized in MDA-MB-231 cancer cells, which also show low dark cytotoxicity and effective photocytotoxicity upon 793 nm excitation. These nanocomposites could be further optimized and are potentially good candidates as nanotheranostics, as well as for other light-conversion applications.

Engineering the Compositional Architecture of Core‐Shell Upconverting Lanthanide‐Doped Nanoparticles for Optimal Luminescent Donor in Resonance Energy Transfer: The Effects of Energy Migration and Storage

“…shell NPs, [21,27,47,90,91] and/or iii) using passive-core-active-shell NPs with shell Di ions exposed at the surface. [23,28,92] Other distance-dependent mechanisms were also proposed and/ or experimentally verified, such as iv) photon avalanche, [93] v) core-shell designs, which exploits upconverted energy diffusion through Gd 3+ network to Tb 3+ or Eu 3+ RET donor ions, [54,59,64] or vi) dye-sensitized UC with tightly packed 800CW dye antenna anchored to the surface, which combined low energy migration zone, antenna enhanced absorption, limiting exposure of Yb 3+ and Er 3+ to surface quenchers.…”

“…[ 61,88 ] These studies evaluated i) increased surface to volume ratio of donor NPs by reducing the size of D filled core NP, aiming to increase the relative number of superficial D i ions per particle. [ 28,89 ] More frequently, distance‐dependent RET from D i to A j was studied by ii) adjusting shell thickness of active core‐passive shell NPs, [ 21,27,47,90,91 ] and/or iii) using passive‐core‐active‐shell NPs with shell D i ions exposed at the surface. [ 23,28,92 ] Other distance‐dependent mechanisms were also proposed and/or experimentally verified, such as iv) photon avalanche, [ 93 ] v) core‐shell designs, which exploits upconverted energy diffusion through Gd 3+ network to Tb 3+ or Eu 3+ RET donor ions, [ 54,59,64 ] or vi) dye‐sensitized UC with tightly packed 800CW dye antenna anchored to the surface, which combined low energy migration zone, antenna enhanced absorption, limiting exposure of Yb 3+ and Er 3+ to surface quenchers.…”

Emitter-Active Shell in NaYF4:Yb,Er/NaYF4:Er Upconversion Nanoparticles for Enhanced Energy Transfer in Photodynamic Therapy

“…TEM images of the UCNPs with different shell thicknesses are presented in Figure S3. The average sizes of UCNPs from CS1 to CS8 were approximately 23,27,32,34,37,42,45, and 55 nm, respectively. The corresponding shell thickness was approximately 0.5, 2.5, 5, 6, 7.5, 10, 11.5, and 16.5 nm, respectively.…”

“…However, the shell can increase the distance between the inner emitters and the photosensitizing molecules at the surface, thus reducing the ET efficiency. The donor–acceptor distance can be shortened by constructing various unique core/shell structures with the emitter also in the shell, such as NaYF 4 :Yb/NaYF 4 :Yb,Er, NaLiF 4 :Yb/NaLiF 4 :Yb,Tm, NaGdF 4 /NaGdF 4 :Yb,Er, NaYF 4 :Nd,Yb/NaYF 4 :Yb/NaYF 4 :Yb,Tm, NaYbF 4 /NaYF 4 :Gd,Er/NaYF 4 :Gd, and NaYF 4 :Nd,Yb/NaYF 4 :Yb/NaYF 4 :Yb,Er/NaYF 4 . Despite these advances, the outermost shell can directly expose the emitter to the external environment or separate the emitter from the surface acceptor, thus reducing the upconversion luminescence and/or the ET efficiency.…”