In this proof-of-concept study (Fig. 1), we hypothesised that HA–HPPS combined with fluorescence/photoacoustic imaging can enable the visualisation of SLNs in a rapid and prolonged manner through size- and charge-dependent passive and active targeting of both CD44 and SR-B1, which can guide the removal of SLNs from patients during breast cancer surgery. This evidence concerns the gene CD44 and breast carcinoma.