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

JOURNAL OF CONTROLLED RELEASE

卷:317

Article

Beguin, Estelle¹  Gray, Michael D.¹  Logan, Keiran A.²  Nesbitt, Heather²  Sheng, Yingjie²  Kamila, Sukanta²  Barnsley, Lester C.³  Bau, Luca¹  McHale, Anthony P.²  Callan, John F.²  Stride, Eleanor¹ 

[1] Univ Oxford, Inst Biomed Engn, Oxford OX3 7DQ, England

[2] Univ Ulster, Biomed Sci Res Inst, Coleraine BT52 1SA, Londonderry, North Ireland

[3] Forschungszentrum Julich, Heinz Maier Leibnitz Zentrum, Julich Ctr Neutron Sci, D-85748 Garching, Germany

关键词: Microbubbles;    Drug delivery;    Magnetic targeting;    Sonodynamic therapy;    Ultrasound;    Medical devices;   

DOI  :  10.1016/j.jconrel.2019.11.013

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free