Biomedical Sciences Research Institute, University of Ulster, Coleraine, Northern Ireland BT52 1SA, UK.
Institute of Biomedical Engineering, University of Oxford, OX3 7DQ, UK.
J Control Release. 2017 Sep 28;262:192-200. doi: 10.1016/j.jconrel.2017.07.040. Epub 2017 Jul 29.
Magnetically responsive microbubbles (MagMBs), consisting of an oxygen gas core and a phospholipid coating functionalised with Rose Bengal (RB) and/or 5-fluorouracil (5-FU), were assessed as a delivery vehicle for the targeted treatment of pancreatic cancer using combined antimetabolite and sonodynamic therapy (SDT). MagMBs delivering the combined 5-FU/SDT treatment produced a reduction in cell viability of over 50% when tested against a panel of four pancreatic cancer cell lines in vitro. Intravenous administration of the MagMBs to mice bearing orthotopic human xenograft BxPC-3 tumours yielded a 48.3% reduction in tumour volume relative to an untreated control group (p<0.05) when the tumour was exposed to both external magnetic and ultrasound fields during administration of the MagMBs. In contrast, application of an external ultrasound field alone resulted in a 27% reduction in tumour volume. In addition, activated caspase and BAX protein levels were both observed to be significantly elevated in tumours harvested from animals treated with the MagMBs in the presence of magnetic and ultrasonic fields when compared to expression of those proteins in tumours from either the control or ultrasound field only groups (p<0.05). These results suggest MagMBs have considerable potential as a platform to enable the targeted delivery of combined sonodynamic/antimetabolite therapy in pancreatic cancer.
磁性响应微泡（MagMBs）由氧气核心和磷脂涂层组成，涂层上功能化了玫瑰红（RB）和/或 5-氟尿嘧啶（5-FU），被评估为联合代谢抑制剂和声动力学疗法（SDT）靶向治疗胰腺癌的药物载体。当在体外对四株胰腺癌细胞系进行测试时，输送联合 5-FU/SDT 治疗的 MagMBs 使细胞活力降低了 50%以上。当在静脉注射 MagMBs 到患有原位人异种移植 BxPC-3 肿瘤的小鼠时，当在 MagMBs 给药期间同时暴露于外部磁场和超声场时，与未治疗的对照组相比，肿瘤体积减少了 48.3%（p<0.05）。相比之下，单独应用外部超声场可使肿瘤体积减少 27%。此外，与对照组或仅超声场组的肿瘤相比，在存在磁场和超声场的情况下用 MagMBs 治疗的动物中收获的肿瘤中，激活的半胱天冬酶和 BAX 蛋白水平均明显升高（p<0.05）。这些结果表明，MagMBs 具有很大的潜力作为平台，可在胰腺癌中实现联合声动力学/代谢抑制剂治疗的靶向递送。
