A novel, metal ion-assisted drug-loading model, in which the metal ion was used to modify the microstructure of DPPC bilayers, has been developed to improve the drug-loading efficiency of cisplatin thermosensitivity liposomes. The reactions of dipalmitoyl phosphatidylcholine (DPPC) with diverse metal ions (Zn2+, Cu2+, Mn2+ and Mg2+) yield four typical liposomes, which have been characterized by FT-IR, Raman and fluorescence techniques; the mechanism for higher drug encapsulation efficiency has also been investigated. In these prepared liposomes, the conformation of DPPC is changed due to the electrostatic interaction between the metal ions and phospholipid acyl group, leading to a closer arrangement of the lipid hydrocarbon chains and higher T-m of DPPC. As a result, the encapsulation efficiency of metal ion-assisted loading liposome is significantly higher than that of metal ion-free state. While for the release time, all four metal ion-assisted liposomes could be released within 10 min at 42 +/- 0.5 degrees C, which approach to the phase transition temperature, indicating that the introduction of metal ions into the DPPC bilayer membranes has no influence on the thermosensitivity of the liposome. Furthermore, the higher cytotoxicity of metal ion-bounded liposomes than that of free cisplatin solution suggests that high encapsulation efficiency can cause cytotoxicity increase. Hence, this work highlighted that metal ion-assisted loading model increased the encapsulation efficiency and cell cytotoxicity of cisplatin in thermosensitive liposomes with no obvious effects on sustained and temperature-dependent drug release. (C) 2015 Elsevier B.V. All rights reserved.