Objective  To investigate the tumor inhibiting effects and relative pharmacodynamics of doxorubicin long-circulating thermo-sensitive liposomes (DOX-LCTSLs) combined with radiofrequency (RF) thermotherapy on HeLa tumor-bearing nude mice.

Methods  A HeLa tumor-bearing mice model was established and the mice were divided into six groups: Control, RF, DOX, DOX-LCTSLs, DOX+RF and DOX-LCTSLs+RF groups. DOX concentration in the organs and tumor were detected at 0.5, 1, 4 and 12 h to determine the biodistribution. During the treatment, the living conditions of the nude mice were observed, the tumor volume was measured every other day and the tumor inhibition rate was calculated. After the treatment, the organs and tumor were stained by HE, and the morphological changes of the cells were observed. TUNEL stained method was used to detect cell apoptosis effect.

Results  Biodistribution results indicated that DOX concentration of DOX-LCTSLs group in the heart was significantly lower than that of DOX group; the tumor inhibition rate of DOX-LCTSLs+RF group was 82.14% which had significant difference compared with DOX and DOX+RF groups (P＜0.05). HE staining results of DOX-LCTSLs group demonstrated that it had no obvious toxicity to major organs, however, the tumor cells appeared irregular and karyolysis; TUNEL apoptosis detection showed that the tumor tissues appeared significant apoptosis after the treatment on DOX-LCTSLs+RF group.

Conclusion  Compared with other treatment groups, DOX-LCTSLs group have the obvious thermal control release effect and low toxicity. With RF thermotherapy treatment, DOX-LCTSLs could significantly enhance the anti-tumor activity.