Control of Luminescence and Interfacial Properties as Perspective for Upconversion Nanoparticles.

Near-infrared (NIR) light is highly suitable for studying biological systems due to its minimal scattering and lack of background fluorescence excitation, resulting in high signal-to-noise ratios. By combining NIR light with lanthanide-based upconversion nanoparticles (UCNPs), upconversion is used to generate UV or visible light within tissue. This remarkable property has gained significant research interest over the past two decades. Synthesis methods are developed to produce particles of various sizes, shapes, and complex core-shell architectures and new strategies are explored to optimize particle properties for specific bioapplications. The diverse photophysics of lanthanide ions offers extensive possibilities to tailor spectral characteristics by incorporating different ions and manipulating their arrangement within the nanocrystal. However, several challenges remain before UCNPs can be widely applied. Understanding the behavior of particle surfaces when exposed to complex biological environments is crucial. In applications where deep tissue penetration is required, such as photodynamic therapy and optogenetics, UCNPs show great potential as nanolamps. These nanoparticles can combine diagnostics and therapeutics in a minimally invasive, efficient manner, making them ideal upconversion probes. This article provides an overview of recent UCNP design trends, highlights past research achievements, and outlines potential future directions to bring upconversion research to the next level.

Bilayer-Coating Strategy for Hydrophobic Nanoparticles Providing Colloidal Stability, Functionality, and Surface Protection in Biological Media.

The surface chemistry of nanoparticles is a key step on the pathway from particle design towards applications in biologically relevant environments. Here, a bilayer-based strategy for the surface modification of hydrophobic nanoparticles is introduced that leads to excellent colloidal stability in aqueous environments and good protection against disintegration, while permitting surface functionalization via simple carbodiimide chemistry. We have demonstrated the excellent potential of this strategy using upconversion nanoparticles (UCNPs), initially coated with oleate and therefore dispersible only in organic solvents. The hydrophobic oleate capping is maintained and a bilayer is formed upon addition of excess oleate. The bilayer approach renders protection towards luminescence loss by water quenching, while the incorporation of additional molecules containing amino functions yields colloidal stability and facilitates the introduction of functionality. The biological relevance of the approach was confirmed with the use of two model dyes, a photosensitizer and a nitric oxide (NO) probe that, when attached to the surface of the UCNPs, retained their functionality to produce singlet oxygen and detect intracellular NO, respectively. We present a simple and fast strategy to protect and functionalize inorganic nanoparticles in biological media, which is important for controlled surface engineering of nanosized materials for theranostic applications.

Small and Bright Water-Protected Upconversion Nanoparticles with Long-Time Stability in Complex, Aqueous Media by Phospholipid Membrane Coating.

Chemical and colloidal stability in complex aqueous media are among the main challenges preventing nanoparticles from successfully entering into the biomedical field. Small core-shell upconversion nanoparticles (UCNPs) NaYF4:Yb,Er@NaYF4 of 12 nm in diameter with a high surface-to-volume ratio are utilized to demonstrate that self-assembling phospholipid bilayers (PLMs) have several benefits compared to common ligand-exchange and ligand-addition particle coatings such as poly(acrylic acid) and amphiphilic polymers. An efficient hydrophobic barrier against water quenching and toward particle disintegration is formed by PLM. Particles with this functionalization have a higher upconversion luminescence in aqueous media in contrast to common surface ligands. They attract with better colloidal stability in phosphate buffer, in a wide pH range, in high ionic solutions, and in complex cell media, as is required for biological applications. Moreover, kidney cells (NRK) are not affected by these stable PLM-coated UCNPs as first cell viability tests reveal.

Plasmonic Enhancement of NIR to UV Upconversion by a Nanoengineered Interface Consisting of NaYF4:Yb,Tm Nanoparticles and a Gold Nanotriangle Array for Optical Detection of Vitamin B12 in Serum.

A nanoengineered interface fabricated by self-assembly enables the online determination of vitamin B12 via a simple luminescence readout in serum without any pretreatment. The interplay of Tm3+-doped NaYF4 nanoparticles (UCNPs) and a gold nanotriangle array prepared by nanosphere lithography on a glass slide is responsible for an efficient NIR to UV upconversion. Hot spots of the gold assembly generate local electromagnetic-field enhancement, favoring the four-photon upconversion process at the low-power excitation of approximately 13 W·cm-2. An improvement by about 6 times of the intensity for the emission peaking at 345 nm is achieved. The nanoengineered interface has been applied in a proof-of-concept sensor for vitamin B12 in serum, which is known as a marker for the risk of cancer; Alzheimer disease; or, during pregnancy, neurological abnormalities in newborn babies. Vitamin B12 can be detected in serum down to 3.0 nmol·L-1 by a simple intensity-based optical readout, consuming only 200 µL of a sample, which qualifies as easy miniaturization for point-of-care diagnostics. Additionally, this label-free approach can be used for long-term monitoring because of the high photostability of the upconversion nanoparticles.