Magnetic microbubble mediated chemo-sonodynamic therapy using a combined magnetic-acoustic device

Magnetic microbubble mediated chemo-sonodynamic therapy using a combined magnetic-acoustic device
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DOI:
10.1016/j.jconrel.2019.11.013
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发表时间:
2020-01-10
影响因子:
10.8
通讯作者:
Stride, Eleanor
Stride, Eleanor
中科院分区:
医学1区
文献类型:
--
作者:
Beguin, Estelle;Gray, Michael D.;Stride, Eleanor

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最近的临床前研究已经证明了联合化疗和声动力学治疗胰腺癌的潜力。载氧磁性微泡已被探索作为该应用的靶向递送载体。尽管初步的积极结果,以前的研究确定了一个重大的实际挑战,关于磁场和超声场的共同对齐。本研究的目的是确定是否可以通过使用磁声装置(MAD)将磁性阵列和超声换能器结合在一个单元中来解决这一挑战,以同时集中和激活靶部位的微泡。在组织模型中进行体外实验,然后在鼠模型中体内治疗异种移植胰腺癌(BxPC-3)肿瘤。在体外,与单独的磁性和超声装置相比,使用MAD实现了模型治疗有效载荷在体模内沉积的1.4倍(p <0.01)增加。在体内,用MAD治疗的肿瘤在治疗后8天的平均体积小了9%,而用单独的装置或单独的微泡治疗的肿瘤分别大了45%和112%。肿瘤体积的这种实质性和持续的减少表明,所提出的药物递送方法有可能成为胰腺癌患者的有效新辅助治疗。
Recent pre-clinical studies have demonstrated the potential of combining chemotherapy and sonodynamic therapy for the treatment of pancreatic cancer. Oxygen-loaded magnetic microbubbles have been explored as a targeted delivery vehicle for this application. Despite preliminary positive results, a previous study identified a significant practical challenge regarding the co-alignment of the magnetic and ultrasound fields. The aim of this study was to determine whether this challenge could be addressed through the use of a magnetic-acoustic device (MAD) combining a magnetic array and ultrasound transducer in a single unit, to simultaneously concentrate and activate the microbubbles at the target site. in vitro experiments were performed in tissue phantoms and followed by in vivo treatment of xenograft pancreatic cancer (BxPC-3) tumours in a murine model. In vitro, a 1.4-fold (p < .01) increase in the deposition of a model therapeutic payload within the phantom was achieved using the MAD compared to separate magnetic and ultrasound devices. In vivo, tumours treated with the MAD had a 9% smaller mean volume 8 days after treatment, while tumours treated with separate devices or microbubbles alone were respectively 45% and 112% larger. This substantial and sustained decrease in tumour volume suggests that the proposed drug delivery approach has the potential to be an effective neoadjuvant therapy for pancreatic cancer patients.