Synthesis of near-infrared-responsive hexagonal-phase upconversion nanoparticles with controllable shape and luminescence efficiency for theranostic applications

Abstract

Over the past few decades, photodynamic therapy has been studied as a therapeutic method by generating singlet oxygen through activation of a photosensitizer (PS) to kill cancer cells. However, the light within the activating wavelength range of commercial photosensitizers has a low penetration depth. In this study, we designed multifunctional upconversion nanoparticles (UCNs) that can emit high-energy light by absorbing low-energy near-infrared (NIR) light with excellent tissue permeability through a fluorescence resonance energy transfer procedure. This process can produce reactive oxygen species by activating the PS. We aimed to optimize the thermal decomposition synthesis procedure to produce lanthanide-doped UCNs with a uniform size and improve the photoluminescence efficiency for an NIR-regulated theranostic system. It was confirmed that the morphologies of UCNs can be controlled by varying the reaction time, reaction temperature, and feed molar ratio of the solvent and reactant. The crystalline morphology of the synthesized UCNs showed a thermodynamically stable hexagonal phase. The photoluminescence efficiency of the UCNs also was influenced by size, surface area, crystalline property, and stability in aqueous solution. Furthermore, the surface-modified UCNs with a folic acid-conjugated block copolymer and PS exhibited enhanced singlet oxygen generation and significantly improved aqueous solubility and photoluminescence efficiency.

Nanomaterials for light-mediated therapeutics in deep tissue

“…To enhance tumour cells uptake of the nanoparticles, targeting ligands like folate have been conjugated on UCNPs. 157,158 Instead of using targeting ligands, magnetic field was shown to increase the cell uptake of transferrin-coated NaYF 4 :Gd 3+ ,Yb 3+ ,Er 3+ loaded with the photosensitizer PpIX on MDA-MB-231 and HeLa cells in vitro . 159 In vivo injection of UCNPs coated with Fe 3 O 4 while placing external magnets near the tumour area also enhanced the accumulation of UCNPs in tumour cells and increased PDT efficacy.…”

NaYF4:Yb/Ho upconversion nanoprobe incorporated gold nanoparticle (AuNP) based FRET immunosensor for the “turn-on” detection of cardiac troponin I

“…This unique anti-Stokes shift property enables its widespread application in the field of biomedicine by avoiding autofluorescence caused by UV-visible excitation in biological samples 23,24 Other key characteristics of the UCNPs are high photostability, deep tissue penetration, chemical stability, large anti-Stokes shift, and a narrow emission peak. 25 Sirkka et al 26 and Raiko et al 27 have fabricated NaYF 4 :Yb,Er based heterogenous UC immunoassays immobilized in streptavidin coated microwells by a biotinylated anti-cTnI monoclonal antibody and a microplate based NaYF 4 :Yb,Er UCNPs sandwich immunoassay for the detection of the cTnI. 26 There are challenges with these immunoassays because of aggregation due to reduction, and non-specific binding interactions with the antibody which necessitates careful optimization conditions for specific detection of cTnI.…”

Effect of Gd3+, La3+, Lu3+ Co-Doping on the Morphology and Luminescent Properties of NaYF4:Sm3+ Phosphors

“…Sodium yttrium fluoride is one of the best host matrices for luminescent rare earth-doped inorganic materials because this matrix has only low-frequency vibrational modes, and therefore does not quench the luminescence. In addition, NaYF 4 possesses chemical inertness, low toxicity, and the possibility to combine magnetic, optical, and radioactive properties of lanthanide ions that opens the way to prepare new theranostic agents for non-invasive therapy [ 17 , 18 , 19 , 20 , 21 , 22 ]. As a co-dopant, lanthanide ions play several key roles in photoluminescent materials: they may absorb light as sensitizers or emit photons as luminescence activators as well as transfer energy from the sensitizer to activator [ 13 , 14 , 23 , 24 , 25 ].…”