Ultrasound-mediated delivery of doxorubicin to the brain results in immune modulation and improved responses to PD-1 blockade in gliomas

Víctor A. Arrieta, Andrew Gould, Kwang-Soo Kim, Karl J. Habashy, Crismita Dmello, Gustavo I. Vázquez-Cervantes, Irina Palacín-Aliana, Graysen McManus, Christina Amidei, Cristal Gomez, Silpol Dhiantravan, Li Chen, Daniel Y. Zhang, Ruth Saganty, Meghan E. Cholak, Surya Pandey, Matthew McCord, Kathleen McCortney, Brandyn Castro, Rachel Ward, Miguel Muzzio, Guillaume Bouchoux, Carole Desseaux, Michael Canney, Alexandre Carpentier, Bin Zhang, Jason M. Miska, Maciej S. Lesniak, Craig M. Horbinski, Rimas V. Lukas, Roger Stupp, Catalina Lee-Chang () and Adam M. Sonabend ()
Additional contact information
Víctor A. Arrieta: Northwestern University
Andrew Gould: Northwestern University
Kwang-Soo Kim: Northwestern University
Karl J. Habashy: Northwestern University
Crismita Dmello: Northwestern University
Gustavo I. Vázquez-Cervantes: Northwestern University
Irina Palacín-Aliana: Northwestern University
Graysen McManus: Northwestern University
Christina Amidei: Northwestern University
Cristal Gomez: Northwestern University
Silpol Dhiantravan: Northwestern University
Li Chen: Northwestern University
Daniel Y. Zhang: Northwestern University
Ruth Saganty: Northwestern University
Meghan E. Cholak: Northwestern University
Surya Pandey: Northwestern University
Matthew McCord: Northwestern University
Kathleen McCortney: Northwestern University
Brandyn Castro: Northwestern University
Rachel Ward: Northwestern University
Miguel Muzzio: IIT Research Institute
Guillaume Bouchoux: Carthera
Carole Desseaux: Carthera
Michael Canney: Carthera
Alexandre Carpentier: Service de Neurochirurgie
Bin Zhang: Northwestern University
Jason M. Miska: Northwestern University
Maciej S. Lesniak: Northwestern University
Craig M. Horbinski: Northwestern University
Rimas V. Lukas: Northwestern University
Roger Stupp: Northwestern University
Catalina Lee-Chang: Northwestern University
Adam M. Sonabend: Northwestern University

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract Given the marginal penetration of most drugs across the blood-brain barrier, the efficacy of various agents remains limited for glioblastoma (GBM). Here we employ low-intensity pulsed ultrasound (LIPU) and intravenously administered microbubbles (MB) to open the blood-brain barrier and increase the concentration of liposomal doxorubicin and PD-1 blocking antibodies (aPD-1). We report results on a cohort of 4 GBM patients and preclinical models treated with this approach. LIPU/MB increases the concentration of doxorubicin by 2-fold and 3.9-fold in the human and murine brains two days after sonication, respectively. Similarly, LIPU/MB-mediated blood-brain barrier disruption leads to a 6-fold and a 2-fold increase in aPD-1 concentrations in murine brains and peritumoral brain regions from GBM patients treated with pembrolizumab, respectively. Doxorubicin and aPD-1 delivered with LIPU/MB upregulate major histocompatibility complex (MHC) class I and II in tumor cells. Increased brain concentrations of doxorubicin achieved by LIPU/MB elicit IFN-γ and MHC class I expression in microglia and macrophages. Doxorubicin and aPD-1 delivered with LIPU/MB results in the long-term survival of most glioma-bearing mice, which rely on myeloid cells and lymphocytes for their efficacy. Overall, this translational study supports the utility of LIPU/MB to potentiate the antitumoral activities of doxorubicin and aPD-1 for GBM.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-48326-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48326-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-48326-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().