A novel approach to a controlled opening of liposomes.

•pH-sensitive liposomes are formed by insertion of amphiphilic activator into bilayer.•Liposomes with activator demonstrate a low cytotoxicity.•Activator changes its orientation in the bilayer adapting to pH of the outer solution.•Rotation of activator is followed by fast release of the cargo from liposomes.•Liposomes, loaded with doxorubicin, are active towards multidrug resistant cells.