Thiol-mediated uptake of phosphorothioate liposomes, visualized with fluorescent flippers.

ABSTRACT: Liposomes made from phosphorothioate lipids are shown to penetrate cells better and differently than conventional phosphodiester liposomes. DSP_SC phosphorothioate liposomes are synthesized, characterized and labeled with either internal doxorubicin or membrane-bound flippers. Inhibition experiments reveal that their penetration of HK cells is independent of endocytosis and occurs by thiol-mediated uptake (TMU). Dynamic covalent exchange with phosphorothioate sulfurs as pseudo-thiolates is confirmed and explored to modify liposomes and activate TMU. Mechanosensitive flipper probes and colocalization experiments reveal that phosphorothioate liposomes cross the plasma membrane in intact form with negligible endocytosis and little fusion. In the cytosol, fast-emitting flipper probes

SUBMITTER: Bouffard J 

PROVIDER: S-EPMC12478204 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature