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Pharmaceutics
Volume 15
Issue 10
10.3390/pharmaceutics15102479
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Communication

Focused Ultrasound-Mediated Delivery of Anti-Programmed Cell Death-Ligand 1 Antibody to the Brain of a Porcine Model

by
Siaka Fadera
1,
Chinwendu Chukwu
1,
Andrew H. Stark
1,
Yimei Yue
1,
Lu Xu
1,
Chih-Yen Chien
1,
Jinyun Yuan
1 and
Hong Chen
1,2,*
1
Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130, USA
2
Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO 63110, USA
*
Author to whom correspondence should be addressed.
Pharmaceutics 2023, 15(10), 2479; https://doi.org/10.3390/pharmaceutics15102479
Submission received: 13 August 2023 / Revised: 1 October 2023 / Accepted: 11 October 2023 / Published: 17 October 2023
(This article belongs to the Special Issue Ultrasound-Mediated Blood–Brain Barrier Disruption and Drug Delivery)
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Abstract

Immune checkpoint inhibitor (ICI) therapy has revolutionized cancer treatment by leveraging the body’s immune system to combat cancer cells. However, its effectiveness in brain cancer is hindered by the blood-brain barrier (BBB), impeding the delivery of ICIs to brain tumor cells. This study aimed to assess the safety and feasibility of using focused ultrasound combined with microbubble-mediated BBB opening (FUS-BBBO) to facilitate trans-BBB delivery of an ICI, anti-programmed cell death-ligand 1 antibody (aPD-L1) to the brain of a large animal model. In a porcine model, FUS sonication of targeted brain regions was performed after intravenous microbubble injection, which was followed by intravenous administration of aPD-L1 labeled with a near-infrared fluorescent dye. The permeability of the BBB was evaluated using contrast-enhanced MRI in vivo, while fluorescence imaging and histological analysis were conducted on ex vivo pig brains. Results showed a significant 4.8-fold increase in MRI contrast-enhancement volume in FUS-targeted regions compared to nontargeted regions. FUS sonication enhanced aPD-L1 delivery by an average of 2.1-fold, according to fluorescence imaging. In vivo MRI and ex vivo staining revealed that the procedure did not cause significant acute tissue damage. These findings demonstrate that FUS-BBBO offers a noninvasive, localized, and safe delivery approach for ICI delivery in a large animal model, showcasing its potential for clinical translation.
Keywords: focused ultrasound; immunotherapy; immune checkpoint inhibitors; blood-brain barrier; brain drug delivery focused ultrasound; immunotherapy; immune checkpoint inhibitors; blood-brain barrier; brain drug delivery

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MDPI and ACS Style

Fadera, S.; Chukwu, C.; Stark, A.H.; Yue, Y.; Xu, L.; Chien, C.-Y.; Yuan, J.; Chen, H. Focused Ultrasound-Mediated Delivery of Anti-Programmed Cell Death-Ligand 1 Antibody to the Brain of a Porcine Model. Pharmaceutics 2023, 15, 2479. https://doi.org/10.3390/pharmaceutics15102479

AMA Style

Fadera S, Chukwu C, Stark AH, Yue Y, Xu L, Chien C-Y, Yuan J, Chen H. Focused Ultrasound-Mediated Delivery of Anti-Programmed Cell Death-Ligand 1 Antibody to the Brain of a Porcine Model. Pharmaceutics. 2023; 15(10):2479. https://doi.org/10.3390/pharmaceutics15102479

Chicago/Turabian Style

Fadera, Siaka, Chinwendu Chukwu, Andrew H. Stark, Yimei Yue, Lu Xu, Chih-Yen Chien, Jinyun Yuan, and Hong Chen. 2023. "Focused Ultrasound-Mediated Delivery of Anti-Programmed Cell Death-Ligand 1 Antibody to the Brain of a Porcine Model" Pharmaceutics 15, no. 10: 2479. https://doi.org/10.3390/pharmaceutics15102479

APA Style

Fadera, S., Chukwu, C., Stark, A. H., Yue, Y., Xu, L., Chien, C.-Y., Yuan, J., & Chen, H. (2023). Focused Ultrasound-Mediated Delivery of Anti-Programmed Cell Death-Ligand 1 Antibody to the Brain of a Porcine Model. Pharmaceutics, 15(10), 2479. https://doi.org/10.3390/pharmaceutics15102479

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