Since DOPC liposomes provided the highest SERS enhancement, this formulation was then selected for further investigation. Both liposome and 4-MBA concentrations were systematically varied to explore Raman features and maximize SERS signals. concentrations (Figure ) and varying 4-MBA content within the vesicles (Figure ). It is remarkable that in both cases SERS enhancement trends were not monotonous, as AuNPs/vesicles ratio or 4-MBA concentration were increased. This effect originates in the subtle mechanistic details of AuNPs-lipid vesicles interaction, elucidated in recent studies and further discussed in the SI, section S3. However, with the insights gained from this understanding, it was possible to inform the design of LipoGold tags, by tuning and controlling the aggregation of AuNPs on 4-MBA-loaded DOPC vesicles. This optimization included the selection of the balance between RRs amount, liposome concentration, particle aggregation extent, and resulting SERS signal. Eventually, the best outcomes were observed for a 1.2 nM liposomal concentration and a 1% MBA content. Interestingly, as elucidated in the next paragraph, these optimal conditions proved effective for other RRs (see also section S4 and S5 of the SI), underlying the broad applicability of this strategy, i.e., its potential application for diverse RRs through the same synthetic approach and in the same experimental conditions.