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

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

Journal of controlled release : official journal of the Controlled Release Society (2019-11-17)
Estelle Beguin, Michael D Gray, Keiran A Logan, Heather Nesbitt, Yingjie Sheng, Sukanta Kamila, Lester C Barnsley, Luca Bau, Anthony P McHale, John F Callan, Eleanor Stride
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
1,2-Distearoyl-sn-glycero-3-phosphoethanolamine, ≥99%
Avanti
18:0 PEG2000 PE, Avanti Polar Lipids 880120C
Avanti
18:0 PEG2000 PE, Avanti Polar Lipids
Avanti
22:0 PC, 1,2-dibehenoyl-sn-glycero-3-phosphocholine, powder
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DSPE-PEG(2000) Biotin, Avanti Polar Lipids 880129P, powder
Avanti
DSPE-PEG(2000) Biotin, Avanti Polar Lipids 880129C
Avanti
22:0 PC, 1,2-dibehenoyl-sn-glycero-3-phosphocholine, chloroform