A gallate derivative with three propargyl groups was coupled to palmitoyl oleoyl phosphoethanolamine (POPE). The resulting anionic lipid was formulated with common lipids such as palmitoyl oleoyl phosphatidyl choline (POPC) to form large unilamellar vesicles (LUVs). Polymerization of the LUVs was accomplished by the Cu(I)-catalyzed click reaction between the propargyl groups and the azide groups in the cross-linker. When the cross-linker contained a disulfide or ketal group, the resulting polymerized liposomes depolymerized and released entrapped contents upon the addition of a reducing thiol or under weakly acidic conditions. The click reaction allowed simultaneous multivalent surface functionalization during cross-linking, making these cleavable polymerized liposomes (CPLs) potentially very useful in the delivery and controlled release of pharmaceutical agents.