Fig. 2

Effect of switch conjugation on hydrophobic cargos. a The switch was conjugated to 9-aminocamptothecin (9AC) and 5,6-dihydro-4H-benzo[de]quinoline-camptothecin (BQC) via a cue-responsive trigger^17,24 to generate 9AC-G^W and BQC-G^W, while it was directly attached to 4-methylumbellirone to generate 4MU-G^W (the red arrows indicate the position where the glycosidic switch was conjugated). The carboxylic acid function of the switch is converted in acidic methanol to a lipid-soluble methylester, which can be reconverted to the water-soluble form in basic aqueous solutions. b Comparison of the water solubility of the parental drugs 9AC and BQC with their water-soluble switch conjugated forms (9AC-G^W and BQC-G^W). Error bars, SD, n = 3. c Kinetics of the conversion of 9AC-G^W to lipid-soluble 9AC-G^L, d BQC-G^W to BQC-G^L and e 4MU-G^W to 4MU-G^L in acidic methanol at 62 °C. The HPLC chromatograms show samples at 0, 15, 30, and 60 min. RFU relative fluorescent units. f Partition coefficients (Log scale) between 50 mM citric acid buffer pH 5 and 1-octanol of the parental compounds compared to their respective -G^W and -G^L forms. Error bars: SD, n = 5. g Stability of 9AC-G^L in liposomal external buffer (50 mM citric acid, 250 mM sodium sulfate, pH 5) at 75 °C. Error bars: SD, n = 3. h Conversion of 9AC-G^L to 9AC-G^W in liposomal internal buffer (50 mM HEPES, 250 mM calcium acetate, pH 8.5) at 75 °C. Error bars: SD, n = 3. Statistical significance of differences in mean values: ***p < 0.0001