Editorial Feature

An Introduction to Upconversion Nanoparticles and Their Applications

Upconversion nanoparticles are an emerging type of fluorophore that can convert low energy photons into high energy photons at a more efficient rate than other materials. Another critical aspect of upconversion nanoparticles is that they are biocompatible and have low cytotoxicity, making them ideal for many biologically-focused applications. In this article, we look at what upconversion nanoparticles are, how they work and some of the areas where they are used.

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What are Upconversion Nanoparticles?

Upconversion nanoparticles are a new generation of fluorophore, relying on both physical and chemical principles to convert photons from a lower energy state to a higher energy state. It is common for these particles to absorb the energy in the infrared (IR) range and to emit the energy in the visible or the ultraviolet (UV) range.

Upconversion nanoparticles are typically composed of inorganic host molecules and a lanthanide dopant embedded within the lattice of the host. Whilst all lanthanides can exhibit some form of upconversion, the absorption and promotion to the desired levels of the visible and UV ranges are only possible with Erbium (III), Holmium (III) and thulium (III), because their inner shell electrons are shielded by the 5s25p6 sub-shells; which creates a large of number of defined energy states. Some upconversion nanoparticles also benefit from extra doping of Ytterbium (III), but the level of doping must be kept below 2 mol% to prevent the loss of excitation energy from occurring through cross-relaxation processes.

How Upconversion Nanoparticles Work

Upconversion nanoparticle mechanisms work differently from other luminescence mechanisms. Most other luminescence processes use a single electron which becomes promoted to the excited state from the ground state. Upconversion nanoparticles, on the other hand, rely on multiple low energy pump photons (intermediate metastates) to accumulate the low energy excitation photons.

Because the only ions possible of the upconversion are select lanthanides with a 3+ charge, this ionization leaves a partially filled 4f electron sub-shell. The lanthanide ions can either act as an emitter that directly gives off light, or a sensitizer that absorbs excited light, upconverts it and transfers it to an emitter (commonly the Ytterbium dopant). Overall, there are five different processes by which the lanthanide ions can upconvert the light by transferring the energy to the emitter; these are excited-state absorption (ESA), energy transfer upconversion (ETU), energy migration upconversion (EMU), cooperative upconversion (CUC) and photon avalanche (PA) mechanisms.

Applications of Upconversion Nanoparticles

Because of their high biocompatibility and small dimensions, upconversion nanoparticles have found most of their use at the interface of biology, medicine, and nanotechnology and are an emerging technology across the interdisciplinary field of nanomedicine. Here we look at a few more specific areas where upconversion nanoparticles are making their mark.

Bioimaging and Labelling

Upconversion nanoparticles possess unique luminescent properties, including high penetration depth into tissues, low background signals, large Stokes shifts, sharp emission bands and low photobleaching that make them an ideal choice for bioimaging and biolabeling applications. They also exhibit low cytotoxicity.

The two-photon absorption mechanism of upconversion nanoparticles means that they produce a higher energy emission and a more efficient upconversion than other technologies, such as those that rely on quantum dots and organic dyes. Additionally, they can be functionalized at the surface; so, when they are the solubilized for use within the body, they retain their luminescence performance. To date, upconversion nanoparticles have been used to image different types of breast cancer cells, HeLa cells, ovarian cancer cells, KB cells, HepG2 cells, and AB12 mouse mesothelioma cells.

Assays and Detection

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Upconversion nanoparticles can be used in both homogeneous and heterogeneous assays. Homogeneous assays using upconversion nanoparticles are usually based on a lanthanide resonance energy transfer (LRET) process between a donor and an acceptor. On the other hand, heterogeneous assays use binding-modulated signals that negate the need for separating unbound labels.

In these assays, the upconversion nanoparticles are used as a luminescent reporter and are known to have been used for affinity assays, immunoassays, and DNA hybridization assays. Upconversion nanoparticles have a low signal to noise ratio that enables them to have enhanced detection limits over other luminescent reporters, and this has been shown to be up to a four-fold increase.

Drug Delivery and Therapeutics

Upconversion nanoparticles have some unique optical properties, such as producing absorption and emission spectra through a forbidden 4f-4f electron transition, which provide long-lifetime and tunable emissions that can be utilized for drug delivery approaches.

Drug delivery strategies that combine upconversion nanoparticles with other biocompatible materials have been tried and tested, and usually involve either a mesoporous silica shell, hydrophobic pockets or hollow spheres with a mesoporous surface. They can also be conjugated with doxorubicin for anti-cancer applications and can be used in conjunction with the plasmonic nanoparticle to convert near infra-red (NIR) light into heat for photothermal therapy treatments. Another area is the coupling of upconversion nanoparticles with photosensitizer molecules for photodynamic therapies to kill tumors and various diseases.


  • Creative Diagnostics: https://www.cd-bioparticles.com/t/Properties-and-Applications-of-Upconversion-Nanoparticles_58.html
  • “Upconversion nanoparticles: synthesis, surface modification and biological applications”- Wang M. D. et al., Nanomedicine: Nanotechnology, Biology and Medicine, 2011, DOI: 10.1016/j.nano.2011.02.013
  • “Lanthanide upconversion nanoparticles and applications in bioassays and bioimaging: A review”- DaCosta M. V. et al., Analytica Chima Acta, 2014, DOI: 10.1016/j.aca.2014.04.030
  • “Upconversion nanoparticles in biological labeling, imaging, and therapy”- Wang F. et al., Analyst, 2010, DOI: 10.1039/c0an00144a

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Liam Critchley

Written by

Liam Critchley

Liam Critchley is a writer and journalist who specializes in Chemistry and Nanotechnology, with a MChem in Chemistry and Nanotechnology and M.Sc. Research in Chemical Engineering.


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