Clinical effect of ultrasound-guided injection of biodegradable poly(lactic-co-glycolic acid)-Fe3O4 in situ implant for magnetic thermal ablation in treatment of nude mice with human liver cancer SMMC-7721 cells

Abstract

Objective: To prepare the Fe3O4-loaded biodegradable liquid-solid phase inversion poly(lactic-co-glycolic acid) (PLGA) in situ implant for ultrasound-guided injection into nude mouse tumor model, and to investigate its clinical effect in thermomagnetic treatment of nude mice with human liver cancer SMMC-7721 cells in an alternating magnetic field. Methods: An in situ implant containing 10% Fe3O4 was prepared, and 50 μl Fe3O4-PLGA-NMP gel was injected into the subcutaneous tissue of Kunming mice. The degradation of this material was observed for 2 consecutive months, and the changes in body weight were recorded. HE staining and Prussian blue staining were performed for the heart, liver, spleen, lung, and kidney of Kunming mice. Fresh ex vivo bovine liver was taken and cut into cubes with a dimension of 2 cm×2 cm×2 cm and then 50 μl Fe3O4-PLGA-NMP gel was injected; after phase inversion, the cubes of ex vivo bovine liver were heated for 1, 2, 3, 4, and 5 minutes, respectively, and then cut open for observing the range of ablation; HE staining was also performed. Micro-CT scan was performed after ultrasound-guided injection of 50 μl Fe3O4-PLGA gel into the tumors of the nude mice, and then the nude mice were divided into treatment group and control group. The mice in the treatment group were given thermomagnetic treatment for 3 minutes, and tumor growth was observed daily. Results: The biodegradation of Fe3O4-PLGA-NMP implant showed that the subcutaneously injected material was gradually metabolized at 2 weeks after injection and that the nude mice were in good condition. The bovine liver ablation experiment showed that the range of ablation of 50 μl Fe3O4-PLGA implant reached 1.46 ± 0.11 cm. HE staining showed that part of bovine liver had coagulative necrosis. The phase inversion experiment of Fe3O4-PLGA gel showed quick liquid-solid phase inversion of the material after injection into the tumor, and the process of liquid-solid phase inversion could be monitored by ultrasound and CT. The detachment and incrustation of the tumor started at 2 days after treatment, the wound started to heal 15 days later, and the tumor tissue disappeared completely. Conclusion: Ultrasound-guided injection of biodegradable Fe3O4-PLGA in situ implant combined with magnetic thermal ablation can effectively treat human liver cancer SMMC-7721 cells in nude mice.