Marano Francesca, Frairia Roberto, Rinella Letizia, Argenziano Monica, Bussolati Benedetta, Grange Cristina, Mastrocola Raffaella, Castellano Isabella, Berta Laura, Cavalli Roberta, Catalano Maria Graziella
Department of Medical SciencesUniversity of Turin, Turin, Italy.
Department of Drug Science and TechnologyUniversity of Turin, Turin, Italy.
Endocr Relat Cancer. 2017 Jun;24(6):275-286. doi: 10.1530/ERC-17-0045. Epub 2017 May 9.
Anaplastic thyroid cancer is one of the most lethal diseases, and a curative therapy does not exist. Doxorubicin, the only drug approved for anaplastic thyroid cancer treatment, has a very low response rate and causes numerous side effects among which cardiotoxicity is the most prominent. Thus, doxorubicin delivery to the tumor site could be an import goal aimed to improve the drug efficacy and to reduce its systemic side effects. We recently reported that, in human anaplastic thyroid cancer cell lines, combining doxorubicin-loaded nanobubbles with extracorporeal shock waves, acoustic waves used in lithotripsy and orthopedics without side effects, increased the intracellular drug content and cytotoxicity. In the present study, we tested the efficacy of this treatment on a human anaplastic thyroid cancer xenograft mouse model. After 21 days, the combined treatment determined the greatest drug accumulation in tumors with consequent reduction of tumor volume and weight, and an extension of the tumor doubling time. Mechanistically, the treatment induced tumor apoptosis and decreased cell proliferation. Finally, although doxorubicin caused the increase of fibrosis markers and oxidative stress in animal hearts, loading doxorubicin into nanobubbles avoided these effects preventing heart damage. The improvement of doxorubicin anti-tumor effects together with the prevention of heart damage suggests that the combination of doxorubicin-loaded nanobubbles with extracorporeal shock waves might be a promising drug delivery system for anaplastic thyroid cancer treatment.
间变性甲状腺癌是最致命的疾病之一，目前尚无治愈性疗法。阿霉素是唯一被批准用于间变性甲状腺癌治疗的药物，其缓解率极低，且会引发众多副作用，其中心脏毒性最为突出。因此，将阿霉素递送至肿瘤部位可能是一个重要目标，旨在提高药物疗效并减少其全身副作用。我们最近报道，在人源间变性甲状腺癌细胞系中，将负载阿霉素的纳米气泡与体外冲击波（用于碎石术和骨科且无副作用的声波）相结合，可增加细胞内药物含量并提高细胞毒性。在本研究中，我们在人源间变性甲状腺癌异种移植小鼠模型上测试了这种治疗方法的疗效。21天后，联合治疗使肿瘤中的药物蓄积量最大，从而导致肿瘤体积和重量减小，肿瘤倍增时间延长。从机制上讲，该治疗诱导了肿瘤细胞凋亡并降低了细胞增殖。最后，尽管阿霉素会导致动物心脏中纤维化标志物增加和氧化应激，但将阿霉素负载到纳米气泡中可避免这些影响，防止心脏损伤。阿霉素抗肿瘤效果的改善以及对心脏损伤的预防表明，负载阿霉素的纳米气泡与体外冲击波相结合可能是一种有前景的间变性甲状腺癌治疗药物递送系统。
