Fig. 7
From: Reversible glycosidic switch for secure delivery of molecular nanocargos
Environmental and cue-responsive behavior of the glycosidic switch. a Mechanism of cue-responsive triggering by lysosomal enzyme beta-glucuronidase (shown in pink). Enzymatic digestion triggers the degradation of the linker (shown in grey) and release of the parental drug 9AC (shown in green). b Illustration (upper panel) and HPLC analysis (lower panel) of the conversion processes between the different forms of the glycosidic switch using 9AC as an example. HPLC peaks showing conversion of 9AC to 9AC-GW (by chemical synthesis), switching to 9AC-GL in acidic methanol, reconversion to 9AC-GW in the pH 8.5 liposomal internal buffer and regeneration of 9AC by human beta-glucuronidase. RFU relative fluorescent units. c Illustration of cells engineered to express anti-PEG/LDL transmembrane domain (TM domain) chimeric receptors for enhanced endocytosis of PEGylated liposomes followed by triggered release of drug by beta-glucuronidase in lysosomes. d Accumulation of 9AC in the cell culture medium after addition of 9AC-GW liposomes to HCC-36 or MDA-MB468 cells or to empty wells without cells. e Accumulation of 9AC in the culture medium after addition of 9AC-GW liposomes to HCC36 cells or HCC36 cells expressing anti-PEG chimeric receptors. HCC36/anti-PEG cells were also treated with beta-glucuronidase inhibitor or beta-glucuronidase shRNA knockdown before addition of liposomes. Error bars: SD, n = 3. Statistical significance of differences in mean values: n.s not significant, **p < 0.001 and ***p < 0.0001
