Small and Bright Lithium-Based Upconverting Nanoparticles

In the context of light-mediated tumor treatment, the application of ultraviolet (UV) radiation can initiate drug release and photodynamic therapy. However, its limited penetration depth in tissues impedes the subcutaneous applicability of such radiation. On the contrary, near-infrared (NIR) light is not energetic enough to initiate secondary photochemical processes, but can pierce tissues at a significantly greater depth. Upconverting nanoparticles (UCNPs) unify the advantages of both extremes of the optical spectrum, they can be excited by NIR irradiation and emit UV light through the process of upconversion, effective NIR-to-UV generation being attained with UCNPs as large as 100 nm. However, in anticipation of biomedical applications, the size of UCNPs must be greatly minimized to favor their cellular internalization; yet straightforward size reduction negatively affects the NIR-to-UV upconversion efficiency. Herein, we propose a two-step strategy to obtain small yet bright lithium-based UCNPs. First, we synthesized UCNPs as small as 5 nm by controlling the relative amount of coordinating ligands, namely oleylamine (OM) and oleic acid (OA). Although these UCNPs were chemically unstable, particle coarsening via an annealing process in the presence of fresh OA yielded structurally stable and highly monodisperse sub-10 nm crystals. Second, we grew a shell with controlled thickness on these stabilized cores of UCNPs, improving the NIR-to-UV upconversion by orders of magnitude. Particularly in the case of LiYbF4:Tm3+/LiYE4 UCNPs, their NIR-to-UV upconversion surpassed the gold standard 90 nm-sized LiYF4:Tm3+, Yb3+ UCNPs. All in all, these UCNPs show great potential within the biomedical framework as they successfully combine the requirements of small size, deep tissue NIR penetration and bright UV emission.