Preparation and Evaluation of Thermosensitive Liposomes Encapsulating I-125-Labeled Doxorubicin Derivatives for Auger Electron Therapy

Auger electrons (AEs) are very low-energy electrons emitted by radionuclides such as I-125 ((125)I). This energy is deposited across a small distance (<0.5 μm), resulting in high linear energy transfer that is potent for causing lethal damage to cancer cells. Thus, AE-emitting radiotherapeutic agents have great potential for cancer treatment. In this study, thermosensitive liposomes (TSLs) encapsulating (125)I-labeled doxorubicin (DOX) derivatives were developed for Auger electron therapy, targeting the DNA of cancer cells. A radioiodinated DOX derivative [(125)I]5 highly accumulated in the nuclei of cancer cells and showed potent cytotoxicity against Colon 26 cancer cells by AEs. Subsequently, [(125)I]5 was loaded into the TSLs with high encapsulation efficiency. Potent release of [(125)I]5 from TSLs was achieved with heating, whereas a decreased release was observed without heating. Furthermore, TSLs encapsulating [(125)I]5 showed a high uptake in the nuclei at 42 °C for 1 h. We supposed that [(125)I]5 was released by heating at 42 °C and accumulated in the nuclei in the cells. These results suggest that the combination of TSLs encapsulating [(125)I]5 and hyperthermia is an effective cancer therapy.