Biomimetic surface engineering of lanthanide-doped upconversion nanoparticles as versatile bioprobes.

The past decade has witnessed an explosion of interest in the development of luminescent nanoparticles because of their excellent potentials in biomedical application. Most recently, lanthanide ion (Ln) doped upconversion nanoparticles (UCNPs), typically NaMF4:Yb /Ln (M= yttrium or gadolinium, Ln= erbium or thulium), have become an exciting new class of nanophosphors that convert nearinfrared (NIR) excitation light (typically ca. 980 nm) into shorter-wavelength luminescence. The major appeal of bioimaging using UCNPs is that deep tissue penetration as well as high-contrast optical imaging can be achieved owing to the ability to suppress autofluorescence and minimize photodamage to living cells. Furthermore, UCNPs can afford tunable multicolor emission with exceptional photostability. These properties coupled with low toxicity to cells make UCNPs an ideal choice for long-term imaging in vitro and in vivo. Despite these promises, a major challenge in the field of UCNPs is the lack of a general methodology to make waterdispersible, bio-compatible, and functionalizable UCNPs, because they are normally prepared in organic solvents and capped with hydrophobic ligands that lack any functional groups for surface modification; meeting this challenge is a prerequisite for many biomedical applications of this class of materials. Toward this goal, silica coating has been developed to render the UCNPs dispersible in water, but further surface modification steps are still required to attach functional groups on the silica shell for bioconjugation. Oxidation of the capped oleic acid ligands to azelaic acid could make UCNPs both water-dispersible and functionalizable, but the oxidation process produces adventitious MnO2 that can quench the luminescence. [4d] Despite the recent advances in the direct synthesis of water-dispersible UCNPs and in the postsynthesis ligand oxidation with ozone or in the ligand-free treatments to render them water-dispersible and functionalizable, there is a need for a simple and general method for producing biocompatible UCNPs with versatile chemical surface properties that allow coupling of various biomolecules; such bionanomaterials can be used in diverse applications, such as selective sensing or imaging and targeted therapy. Herein, we report such an approach to engineer the UCNP surface coating with a monolayer of functional phospholipids (Figure 1). These phospholipids afford biocompatibility by mimicking the composition and functionality of the cell s external membrane.