Special issue on Upconversion Methods, Applications and Materials

Photodynamic therapy (PDT) is a well-established treatment of cancer that uses the toxic reactive oxygen species, including singlet oxygen (¹O₂), generated by photosensitiser (PS) drugs following irradiation of a specific wavelength to destroy the cancerous cells and tumours. Visible light is commonly used as the excitation source in PDT, which is not ideal for cancer treatment due to its reduced tissue penetration, and thus inefficiency to treat deep-lying tumours. Additionally, these wavelengths exhibit elevated autofluorescence background from the biological tissues which hinders optical biomedical imaging. An alternative to UV–Vis irradiation is the use of near infrared (NIR) excitation for PDT. This can be achieved using upconverting nanoparticles (UCNPs) functionalised with photosensitiser drugs where UCNPs can be used as an indirect excitation source for the activation of PS drugs yielding to the production of singlet ¹O₂ following NIR excitation. The use of nanoparticles for PDT is also beneficial due to their tumour targeting capability, either passively via the enhanced permeability and retention (EPR) effect or actively via stimuli-responsive targeting and ligand-mediated targeting (i.e. using recognition units that can bind specific receptors only present or overexpressed on tumour cells). Here, we review recent advances in NIR upconverting nanomaterials for PDT of cancer with a clear distinction between those reported nanoparticles that could potentially target the tumour due to accumulation via the EPR effect (passive targeting) and nanoparticle-based systems that contain targeting agents with the aim of actively target the tumour via a molecular recognition process.

Anisotropic rare earth ion (RE³⁺) doped fluoride upconversion particles are emerging as potential candidate in diverse areas, ranging from biomedical imaging to photonics. Here, we develop a facile strategy to synthesize NaYF₄: Yb, Gd, Er, and NaYF₄: Yb, Gd, Tm upconversion nanorods via microwave synthesis route by controlling the synthesis time and compared the optical properties similar nanorods prepared via solvothermal technique. With the increase in synthesis time, the phase of the particle found to change from mixed phase to purely hexagonal and morphology of the particles change mixed phase of spherical and rod-shaped particles to completely nanorods for a synthesis time of 60 min. Further, the intrinsically hydrophobic particles changed to hydrophilic by removal of oleic capping via acid treatment and the amine functionalized silica coating. The upconversion luminescence as well as laser power dependent emission properties of the surface modified particles elucidate that surface modification route influence the upconversion luminescence as well as solvent dependent emission properties. Moreover, the laser power dependent studies elucidate that the upconversion process in a multi-photon process.

Upconversion materials have several advantages for many applications due to their great potential in converting infrared light to visible. For practical use, it is necessary to achieve high intensity of UC luminescence, so the studies of the optimal synthesis parameters for upconversion nanoparticles are still going on. In the present work, we analyzed the synthesis temperature effect on the efficiency and luminescence decay of β-NaGd_0.78Yb_0.20Er_0.02F₄ (15–25 nm) upconversion nanoparticles with hexagonal crystal structure synthesized by anhydrous solvothermal technique. The synthesis temperature was varied in the 290 °C–320 °C range. The synthesis temperature was shown to have a significant influence on the upconversion luminescence efficiency and decay time. The coherent scattering domain linearly depended on the synthesis temperature and was in the range 13.1–22.3 nm, while the efficiency of the upconversion luminescence increases exponentially from 0.02 to 0.10% under 1 W cm⁻² excitation. For a fundamental analysis of the reasons for the upconversion luminescence intensity dependence on the synthesis temperature, it was proposed to use the maximum entropy method for luminescence decay kinetics processing. This method does not require a preliminary setting of the number of exponents and, due to this, makes it possible to estimate additional components in the luminescence decay kinetics, which are attributed to different populations of rare-earth ions in different conditions. Two components in the green luminescence and one component in the red luminescence decay kinetics were revealed for nanoparticles prepared at 290 °C–300 °C. An intense short and a weak long component in green luminescence decay kinetics could be associated with two different populations of ions in the surface quenching layer and the crystal core volume. With an increase in the synthesis temperature, the second component disappears, and the decay time increases due to an increase in the number of ions in the crystal core volume and a more uniform distribution of dopants.

A near-infrared (NIR) light-triggered release method for nitric oxide (NO) was developed utilizing core/shell NaYF₄: Tm/Yb/Ca@NaGdF₄: Nd/Yb up-conversion nanoparticles (UCNPs) bearing a mesoporous silica (mSiO₂) shell loaded with the NO donor S-nitroso-N-acetyl-DL-penicillamine (SNAP). To avoid overheating in biological samples, Nd³⁺ was chosen as a sensitizer, Yb³⁺ ions as the bridging sensitizer, and Tm³⁺ ions as UV-emissive activator while co-doping with Ca²⁺ was done to enhance the luminescence of the activator Tm³⁺. NO release from SNAP was triggered by an NIR-UV up-conversion process, initiated by 808 nm light absorbed by the Nd³⁺ ions. NO release was confirmed by the Griess method. Under 808 nm irradiation, the viability of the liver cancer cell line HepG2 significantly decreased with increasing UCNPs@mSiO₂-SNAP concentration. For a UCNPs@mSiO₂-SNAP concentration of 200 μg ml⁻¹, the cell survival probability was 47%. These results demonstrate that UCNPs@mSiO₂-SNAP can induce the release of apoptosis-inducing NO by NIR irradiation.

The increasing interest in upconverting nanoparticles (UCNPs) in biodiagnostics and therapy fuels the development of biocompatible UCNPs platforms. UCNPs are typically nanocrystallites of rare-earth fluorides codoped with Yb³⁺ and Er³⁺ or Tm³⁺. The most studied UCNPs are based on NaYF₄ but are not chemically stable in water. They dissolve significantly in the presence of phosphates. To prevent any adverse effects on the UCNPs induced by cellular phosphates, the surfaces of UCNPs must be made chemically inert and stable by suitable coatings. We studied the effect of various phosphonate coatings on chemical stability and in vitro cytotoxicity of the Yb³⁺,Er³⁺-codoped NaYF₄ UCNPs in human endothelial cells obtained from cellular line Ea.hy926. Cell viability of endothelial cells was determined using the resazurin-based assay after the short-term (15 min), and long-term (24 h and 48 h) incubations with UCNPs dispersed in cell-culture medium. The coatings were obtained from tertaphosphonic acid (EDTMP), sodium alendronate and poly(ethylene glycol)-neridronate. Regardless of the coating conditions, 1 − 2 nm-thick amorphous surface layers were observed on the UCNPs with transmission electron microscopy. The upconversion fluorescence was measured in the dispersions of all UCNPs. Surafce quenching in aqueous suspensions of the UCNPs was reduced by the coatings. The dissolution degree of the UCNPs was determined from the concentration of dissolved fluoride measured with ion-selective electrode after the ageing of UCNPs in water, physiological buffer (i.e., phosphate-buffered saline—PBS) and cell-culture medium. The phosphonate coatings prepared at 80 °C significantly suppressed the dissolution of UCNPs in PBS while only minor dissolution of bare and coated UCNPs was measured in water and cell-culture medium. The viability of human endothelial cells was significantly reduced when incubated with UCNPs, but it increased with the improved chemical stability of UCNPs by the phosphonate coatings with negligible cytotoxicity when coated with EDTMP at 80 °C.

Recently, the up-converting (UC) materials, containing lanthanide ions (Ln³⁺)have attracted considerable attention because of the multitude of their potential applications. The most frequently investigated are UC systems based on the absorption of near-infrared (NIR) radiation by Yb³⁺ ions at around 975–980 nm and emission of co-dopants, usually Ho³⁺, Er³⁺ or Tm³⁺ ions. UC can be observed also upon excitation with irradiation with a wavelength different than around 980 nm. The most often studied systems capable of UC without the use of Yb³⁺ ion are those based on the properties of Er³⁺ ions, which show luminescence resulting from the excitation at 808 or 1532 nm. However, also other Ln³⁺ ions are worth attention. Herein, we focus on the investigation of the UC phenomenon in the materials doped with Ho³⁺ ions, which reveal unique optical properties upon the NIR irradiation. The SrF₂ NPs doped with Ho³⁺ ions in concentrations from 4.9% to 22.5%, were synthesized by using the hydrothermal method. The structural and optical characteristics of the obtained SrF₂:Ho³⁺ NPs are presented. The prepared samples had crystalline structure, were built of NPs of round shapes and their sizes ranged from 16.4 to 82.3 nm. The NPs formed stable colloids in water. Under 1156 nm excitation, SrF₂:Ho³⁺ NPs showed intense UC emission, wherein the brightest luminescence was recorded for the SrF₂:10.0%Ho³⁺ compound. The analysis of the measured lifetime profiles and dependencies of the integral luminescence intensities on the laser energy allowed proposing the mechanism, responsible for the observed UC emission. It is worth mentioning that the described SrF₂:Ho³⁺ samples are one of the first materials for which the UC luminescence induced by 1156 nm excitation was obtained.

In this work we use lanthanide based NaYF₄:Er³⁺, Yb³⁺ upconversion nanoparticles (UCNP) to detect ppb-level sensitibity of a xanthene dye, Rhodamine B (RB) dye, under NIR excitation. A static energy transfer was observed between the luminescent UCNP energy donors and RB acceptor in aqueous solution for three different sizes of UCNP. No specific covalent functionalization of the UCNPs was performed providing a direct method of detection, particularly promising in natural systems where the interfering fluorescence background is a detrimental limitation to the performance of the detection method. This procedure is a first approach to be applied in estuarine and coastal zone where the high content of suspended particulate matter prevents the detection of tracers.