OncoTargets and Therapy (Aug 2016)
Docetaxel-loaded lipid microbubbles combined with ultrasound-triggered microbubble destruction for targeted tumor therapy in MHCC-H cells
Abstract
Yue Zhang,1,* Ruijiao Chang,1,* Muqiong Li,2,* Kun Zhao,3 Hongzhi Zheng,4 Xiaodong Zhou1 1Department of Ultrasound, Xijing Hospital, 2Department of Chemistry, School of Pharmacy, Fourth Military Medical University, Xi’an, 3Department of Cardiothoracic Surgery, The Third Chinese People’s Liberation Army Hospital, Baoji, Shaanxi Province, 4Department of Ultrasound, The 534 Hospital, Luoyang, Henan Province, People’s Republic of China *These authors contributed equally to this work 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. Keywords: lipid microbubble, liver cancer, docetaxel, ultrasound-triggered drug delivery
