The
strong upconversion luminescence (UCL) of upconversion nanoparticles
(UCNPs) endows the nanoparticles with attractive features for combined
imaging and drug delivery. UCNPs convert near-infrared (NIR) light
into light of shorter wavelengths such as light in the ultraviolet
(UV) and visible regions, which can be used for light-guided drug
delivery. Although light-responsive drug delivery systems as such
have been known for many years, their application in medicine is limited,
as strong UV-light can be damaging to tissue; moreover, UV light will
not penetrate deeply into the skin, an issue that UCNPs can now address.
However, UCNPs, as obtained after synthesis, are usually hydrophobic
and require further surface functionalization to be stable in plasma.
Polymers can serve as versatile surface coatings, as they can provide
good colloidal stability, prevent the formation of a protein corona,
provide a matrix for drugs, and be stimuli-responsive. In this Review,
we provide a brief overview of the most recent progress in the synthesis
of UCNPs with different shapes/sizes. We will then discuss the purpose
of polymer coating for drug delivery before summarizing the strategies
to coat UCNPs with various polymers. We will introduce the different
polymers that have so far been used to coat UCNPs with the purpose
to create a drug delivery system, focusing in detail on light-responsive
polymers. To expand the application of UCNPs to allow photothermal
therapy or magnetic resonance imaging (MRI) or to simply enhance the
loading capacity of drugs, UCNPs were often combined with other materials
to generate multifunctional nanoparticles such as carbon-based NPs
and nanoMOFs. We then conclude with a discussion on drug loading and
release and summarize the current knowledge on the toxicity of these
polymer-coated UCNPs.