Fluorescent lipid nanoemulsions (LNEs), owing to their biocompatibility, good in vivo stability, and
low toxicity, have found applications in biomedical imaging [1]. However, their targeting to specific
cells remains challenging because of difficulties in functionalizing them [2]. Here, we have developed
an approach to functionalize LNEs with antibodies by inserting an azide linker (NH2-PEG-N3) via
in situ reaction with a cholesterol derivative inside LNEs. Azide-LNEs were further decorated with
antibodies bearing “clickable” DBCO group and tested in cancer cells. Fluorescence microscopy
showed selective accumulation of Cy5.5-loaded LNEs in HER2-positive cells. Our approach offers a
plug-and-play fluorescent nano-platform for cellular targeting in cancer and cardiovascular diseases.