Applications in Theranostics Guanying Chen,*,†,‡ Hailong Qiu,†,‡ Paras N. Prasad,*,‡,§ and Xiaoyuan Chen* †School of Chemical Engineering and Technology, Harbin Institute of Technology, Harbin, Heilongjiang 150001, China ‡Department of Chemistry and the Institute for Lasers, Photonics, and Biophotonics, University at Buffalo, State University of New York, Buffalo, New York 14260, United States Department of Chemistry, Korea University, Seoul 136-701, Korea Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland 20892-2281, United States

Upconversion Nanoparticles: Design, Nanochemistry, and Applications in Theranostics

Rare-earth upconversion nanophosphors (UCNPs), when excited by continuous-wave near-infrared light, exhibit a unique narrow photoluminescence with higher energy. Such special upconversion luminescence makes UCNPs promising as bioimaging probes with attractive features, such as no auto-fluorescence from biological samples and a large penetration depth. As a result, UCNPs have emerged as novel imaging agents for small animals. In this critical review, recent reports regarding the synthesis of water-soluble UCNPs and their surface modification and bioconjugation chemistry are summarized. The applications of UCNPs for small-animal imaging, including tumor-targeted imaging, lymphatic imaging, vascular imaging and cell tracking are reviewed in detail. The exploration of UCNPs as multifunctional nanoscale carriers for integrated imaging and therapy is also presented. The biodistribution and toxicology of UCNPs are further described. Finally, we discuss the challenges and opportunities in the development of UCNP-based nanoplatforms for small-animal imaging (276 references).

Upconversion nanophosphors for small-animal imaging

Synthesis, Luminescent Properties, and Biomedical Applications Shili Gai,†,‡ Chunxia Li,† Piaoping Yang,*,‡ and Jun Lin*,† †State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China ‡Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, Harbin Engineering University, Harbin, 150001, P. R. China

Recent Progress in Rare Earth Micro/Nanocrystals: Soft Chemical Synthesis, Luminescent Properties, and Biomedical Applications

Lanthanide pairs, which can upconvert low energy photons into higher energy photons, are promising for efficient upconversion emission. A typical system with Yb3+ as a sensitizer can convert short NIR into visible/ultraviolet light via energy transfer between lanthanide ions. Such upconverting nanocrystals doped with lanthanide ions have found significant potential in bioimaging, photochemical reactions and energy conversion. This review presents a fundamental understanding of energy transfer in lanthanide-supported photon upconversion. We introduce the emerging progress in excitation selection based on the energy transfer within lanthanide ions or activation from antennae, with an outlook in the development and applications of the lanthanide upconversion emissions.

Energy transfer in lanthanide upconversion studies for extended optical applications

Lanthanide-doped upconversion nanoparticles (UCNPs) have attracted considerable interest due to their superior physicochemical features, such as large anti-Stokes shifts, low autofluorescence background, low toxicity and high penetration depth, which make them extremely suitable for use as alternatives to conventional downshifting luminescence bioprobes like organic dyes and quantum dots for various biological applications. A fundamental understanding of the photophysics of lanthanide-doped UCNPs is of vital importance for discovering novel optical properties and exploring their new applications. In this review, we focus on the most recent advances in the development of lanthanide-doped UCNPs as potential luminescent nano-bioprobes by means of our customized lanthanide photophysics measurement platforms specially designed for upconversion luminescence, which covers from their fundamental photophysics to bioapplications, including electronic structures (energy levels and local site symmetry of emitters), excited-state dynamics, optical property designing, and their promising applications for in vitro biodetection of tumor markers. Some future prospects and efforts towards this rapidly growing field are also envisioned.

Lanthanide-doped upconversion nano-bioprobes: electronic structures, optical properties, and biodetection

Effectively Utilizing NIR Light Using Direct Electron Injection from Up-Conversion Nanoparticles to the TiO2 Photoanode in Dye-Sensitized Solar Cells

Here we elucidate the “cooperative effect” of carboxylic acid/amine on the size, shape, and multicolor output of fluoride upconversion nanoparticles (UCNPs) utilizing the amidation reaction. During the synthesis of NaYF4 UCNPs using oleic acid (OA) and octadecylamine (OM) as ligands, the evolution of the reaction solution was monitored by FT-IR and proton nuclear magnetic resonance (1H-NMR) spectroscopy. It is shown that N-octadecyloleamide (OOA) was formed and tightly bonded to the surface of the fluoride UCNPs. FT-IR and 1H-NMR analyses point towards a two-step OOA formation mechanism where OA initially reacted with OM to form an acid–base complex (C17H33CO2− +NH3C18H37) in reaction mixture, which further transformed into OOA before the nucleation of fluoride UCNPs at elevated temperature. Importantly, we find that the interaction of OOA with the surfaces of the fluoride UCNPs was stronger than that of OM, and that OOA could strongly quench the green-emitting levels of excited Er3+ ions. A series of control experiments and analyses demonstrate that OOA was not only responsible for the control of the size and shape of NaYF4: 20% Yb, 2% Er UCNPs, but also for the multicolor tuning of them. Those observations reveal that the “cooperative effect” between carboxylic acid and amine results from the amidation reaction and its product. This paper provides us with some new deep insights into the “cooperative effect” of carboxylic acid and amine during the synthesis of inorganic nanoparticles under thermolysis. Furthermore, other lanthanide-ion doped fluoride UCNPs with controlled size, shape and multicolor output can also be obtained in the same way.

Utilizing the amidation reaction to address the “cooperative effect” of carboxylic acid/amine on the size, shape, and multicolor output of fluoride upconversion nanoparticles

Due to the strong tissue absorption of short-wave-length light below 600 nm, in vivo imaging based on UCNPs as luminescent probes is still limited. The NIR spectral range (700–1100 nm) and the red region (600–700 nm) are referred to as the “optical window” of the biological tissues because the light scattering, absorbance and autofluorescence of tissue are minimum in this range. Here we synthesized NaYF4:Yb3+,Tm3+/CdS nanoheterostructures. In the nanoheterostructures, the red (700 nm) and NIR (802 nm) emissions of NaYF4:Yb,Tm were enhanced by 7.3 times, while the blue emission peak at 476 nm nearly disappeared and no peak of CdS appeared. Transmission electron microscopy (TEM) images show that the morphology of the binary nanoparticles is predominantly peanut-like and the X-ray diffraction (XRD) patterns of the NaYF4:Yb3+,Tm3+/CdS nanoheterostructure were assignable to both wurtzite phase CdS and hexagonal phase NaYF4:Yb3+,Tm3+. In comparison, introducing Cd2+ ions or S2− ions or preparation of physical mixture of NaYF4:Yb3+,Tm3+ and CdS did not enhance the red (700 nm) and NIR (802 nm) emissions of NaYF4:Yb, Tm. These results indicated that the interactions in the NaYF4:Yb3+,Tm3+/CdS nanoheterostructure played a key role for enhancing the NIR emission of NaYF4:Yb3+,Tm3+ nanocrystals. QDs act as a sub energy level to mediate energy transfer of Tm3+. To evaluate the effect of other QDs on the upconverted fluorescence spectrum of NaYF4:Yb3+,Tm3+, NaYF4:Yb3+,Tm3+/CdSe nanoheterostructures were also prepared by a similar method. The upconverted fluorescence spectra indicated that by conjugation with CdSe, the NIR emission at 802 nm of NaYF4:Yb3+,Tm3+ was also enhanced greatly.

Strong red and NIR emission in NaYF4:Yb3+,Tm3+/QDs nanoheterostructures

Upconversion photoluminescence enhancement and modulation of NaYF4:Yb, Er through using different ligands

In this work, the ligand dynamic effect was utilized to synthesize hexagonal NaYF4 (β-NaYF4) crystals with controllable morphology by a hydrothermal method. A series of fatty acids was chosen as organic ligands to investigate the ligand dynamic effect on the crystal morphology. Confirmed by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray power diffraction (XRD), the dynamic nature of ligands has strong influences on the crystal morphology, crystal growth and phase transition processes. Moreover, possible crystal growth processes with different chain length ligands have been proposed.

Suli Wu

Papers

Effectively Utilizing NIR Light Using Direct Electron Injection from Up-Conversion Nanoparticles to the TiO2 Photoanode in Dye-Sensitized Solar Cells

Utilizing the amidation reaction to address the “cooperative effect” of carboxylic acid/amine on the size, shape, and multicolor output of fluoride upconversion nanoparticles

Strong red and NIR emission in NaYF4:Yb3+,Tm3+/QDs nanoheterostructures

Upconversion photoluminescence enhancement and modulation of NaYF4:Yb, Er through using different ligands

Ligand dynamic effect on phase and morphology control of hexagonal NaYF4