We then used electron microscopy to probe physical and compositional changes during the ligand exchange process (Figure ). After carrying out a direct Sn2S6 4-exchange, we observe a decrease of about 2 nm in the average center-to-center distance of the UCNPs, confirming that the bulkier oleate has been replaced by more compact Sn2S6 4-. EDS elemental mapping showed that sulfur and tin were uniformly dispersed among the UNCPs at both the nanoscale (Figure and S2) and microscale (Figure ). In summary, all analyses validate that NaYF4 UCNPs can be effectively functionalized with Sn2S6 4-ligands through either direct or indirect ligand exchange approaches. However, the indirect exchange gives a significantly higher yield and hence was our preferred method for subsequent experiments.