Docetaxel-loaded lipid microbubbles combined with ultrasound-triggered microbubble destruction for targeted tumor therapy in MHCC-H cells

Abstract

Background: Efficient and targeted delivery of cytotoxic drugs is still a challenge in the fight against cancer. Ultrasound-targeted destruction of cytotoxic drug-loaded lipid microbubbles (LMs) might be a promising method. This study aimed to explore the antitumor effects of docetaxel-loaded LM (DLLM) combined with ultrasound-targeted microbubble destruction (UTMD) on liver cancer. Materials and methods: DLLMs were made by a mechanical vibration technique. The effects of docetaxel, DLLM alone, and DLLM + UTMD on cell viability and cell proliferation (Cell Counting Kit-8 assay) of MHCC-H cells and HepG2 cells were tested. The effects on cell cycle (flow cytometry) and apoptosis (flow cytometry and immunoblotting) of MHCC-H cells were tested. Solid fast-growing tumor mouse models were established and were randomized to blank LM + UTMD (controls) or DLLM + UTMD. Tumor volume was compared between the two groups. Results: DLLMs had an 18%±7% drug-loading capacity, an 80%±3% encapsulation efficiency, and a mean particle size of 2,845 nm (75% range 1,527–5,534 nm). Compared to the other groups, DLLM + UTMD decreased the proliferation and increased the apoptosis of MHCC-H cells. DLLM + UTMD resulted in the inhibition of a higher proportion of cells in the G1 phase. Compared to the control group, the tumor volume in mice receiving DLLM + UTMD was smaller. Conclusion: DLLM + UTMD can increase the proportion of cells arrested in the G1 phase, decrease tumor cell proliferation, and induce MHCC-H cell apoptosis. The growth of solid tumors in mice was inhibited. These results could provide a novel targeted strategy against liver cancer.