In this paper, hybrid vesicles assembled from hydrophilic graft copolymer sodium alginate-g-poly (N-isopropylacrylamide) (ALG-g-PNIPAM) and multivalent metal ions (Ca2+ and Al3+) for controlled release of 5-Fluorouracil (5-FU) were studied. Transmission electron microscopy (TEM) showed that the vesicles had a well-defined hollow structure with a size of about 100 nm. The hydrophobic membrane was formed by the negatively charged sodium alginate cross-linked with metal ions, and the diffuse corona was constituted of swollen neutral polymer chains. The high stability of vesicles was the result of the nature of coordination complex bonds between anionic sodium alginate chains and metal ions. The lower critical solution temperature (LCST) of polymer vesicles was in the region of 37 degrees C. The drug loading efficiency of hybrid vesicles was high due to the large cavities of hollow structure and intermolecular attractions with drug. Changing temperature, pH or ionic strength, a sustained and controlled drug release was observed. The novel hybrid polymer vesicles are expected to be used in the field of intelligent drug delivery system. (C) 2014 Elsevier B.V. All rights reserved.