Evaluation of efficacy of tumor-specific nanoliposomal radiosensitizer in radiotherapy

Abstract

Radiotherapy is one of the cancer treatment options in which ionizing radiation is used. While the ionizing radiation used here damages the tumor cells, it also damages the surrounding healthy cells and tissues. One of the approaches used to reduce the undesirable side effects and increase the therapeutic efficacy of radiotherapy is the use of radiosensitizers. Up to now, different radiosensitizers have been investigated for this purpose and recently, nanotechnology-based radiosensitizer research has attracted much attention. In this study, the therapeutic efficacy of tumor-targeted, nano-sized liposomal radiosensitizers containing quantum dots-photosensitizer conjugate was evaluated in vivo. It was aimed to destroy more tumor cells by using same the radiation doses routinely used in cancer treatment in radiation oncology clinics or to destroy about the same amount of tumor cells by using lower radiation doses than the routinely used clinical dose. For this purpose, nano-sized, PEG-coated, and folic acid-modified tumor-specific liposomes loaded with quantum dots (QD = CdSe/ZnS) - photosensitizer (Ce6 = Clorine-e6) conjugate was prepared and their therapeutic efficacy was evaluated in 4T1 murine breast cancer cell tumor-bearing mice. Following the single dose of 10Gy 6 MV X-ray irradiation after administration of liposomal radiosensitizer, changes in animals' weights and tumor volumes were measured and animal survival was monitored to evaluate the efficacy of the treatment. Histopathological studies were also performed to examine possible damage to the tumor and normal tissues. In control groups, only X-ray irradiation was applied or no treatment was applied to mice. The results showed that the liposomal radiosensitizer plus radiotherapy killed more cancer cells than radiotherapy alone. While tumor volumes increased in the control group, approximately a 39% reduction in tumor volumes was observed in mice treated with x-ray irradiation following administration of the liposomal radiosensitizer. The obtained results showed that nano-sized liposomal radiosensitizers could be a promising radiosensitizer to achieve better treatment efficacy in radiotherapy by applying fewer radiation doses compared to clinically used radiation doses.