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

Doxorubicin / pharmacology Animals Humans Programmed Cell Death 1 Receptor / antagonists & inhibitors Mice Blood-Brain Barrier / metabolism Brain Neoplasms / drug therapy Microbubbles Cell Line, Tumor Glioma / drug therapy Brain / metabolism Female Drug Delivery Systems Ultrasonic Waves Glioblastoma / drug therapy Male Microglia / drug effects Mice, Inbred C57BL Antibodies, Monoclonal, Humanized / therapeutic use Immune Checkpoint Inhibitors / pharmacology Polyethylene Glycols

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
06 Jun 2024
Historique:
received: 08 03 2023
accepted: 29 04 2024
medline: 7 6 2024
pubmed: 7 6 2024
entrez: 6 6 2024
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41467-024-48326-w PMID: 38844770
pubmed: 38844770
doi: 10.1038/s41467-024-48326-w
pii: 10.1038/s41467-024-48326-w
doi:

Substances chimiques

Doxorubicin 80168379AG
Programmed Cell Death 1 Receptor 0
liposomal doxorubicin 0
pembrolizumab DPT0O3T46P
Antibodies, Monoclonal, Humanized 0
Immune Checkpoint Inhibitors 0
PDCD1 protein, human 0
Polyethylene Glycols 3WJQ0SDW1A

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

4698

Subventions

Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : 1R01NS110703-01A1
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : 1U19CA264338-01
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : P50CA221747
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : 1R01CA245969-01A1

Informations de copyright

© 2024. The Author(s).

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Auteurs

Víctor A Arrieta (VA)

Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
PECEM, Facultad de Medicina, Universidad Nacional Autónoma de Mexico, Mexico City, Mexico.

Andrew Gould (A)

Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Kwang-Soo Kim (KS)

Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Karl J Habashy (KJ)

Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Crismita Dmello (C)

Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
ORCID: 0000-0002-1688-9663

Gustavo I Vázquez-Cervantes (GI)

Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Irina Palacín-Aliana (I)

Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Deparment of Radiation Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Graysen McManus (G)

Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
ORCID: 0009-0001-0298-0191

Christina Amidei (C)

Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Cristal Gomez (C)

Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Silpol Dhiantravan (S)

Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Li Chen (L)

Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Daniel Y Zhang (DY)

Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Ruth Saganty (R)

Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Meghan E Cholak (ME)

Department of Medicine, Division of Hematology and Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Surya Pandey (S)

Department of Medicine, Division of Hematology and Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Matthew McCord (M)

Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Deparment of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Kathleen McCortney (K)

Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
ORCID: 0000-0001-7085-830X

Brandyn Castro (B)

Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Rachel Ward (R)

Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Miguel Muzzio (M)

Life Sciences Group, IIT Research Institute, Chicago, IL, USA.

Guillaume Bouchoux (G)

Carthera, Lyon, France.

Carole Desseaux (C)

Carthera, Lyon, France.

Michael Canney (M)

Carthera, Lyon, France.

Alexandre Carpentier (A)

Sorbonne Université, Inserm, CNRS, UMR S 1127, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière-Charles Foix, Service de Neurochirurgie, Paris, France.

Bin Zhang (B)

Department of Medicine, Division of Hematology and Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
ORCID: 0000-0002-6631-7647

Jason M Miska (JM)

Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
ORCID: 0000-0001-9608-2810

Maciej S Lesniak (MS)

Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
ORCID: 0000-0002-0096-5107

Craig M Horbinski (CM)

Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
ORCID: 0000-0001-8340-9992

Rimas V Lukas (RV)

Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Roger Stupp (R)

Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Department of Medicine, Division of Hematology and Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
ORCID: 0000-0002-5483-3118

Catalina Lee-Chang (C)

Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. catalina.leechang@northwestern.edu.
Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. catalina.leechang@northwestern.edu.
ORCID: 0000-0002-7675-2124

Adam M Sonabend (AM)

Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. adam.sonabend@northwestern.edu.
Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. adam.sonabend@northwestern.edu.
ORCID: 0000-0002-8347-1945

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Classifications MeSH

questionsmedicales.fr › Glucides › Hétérosides › Aminosides › Anthracyclines › Daunorubicine › Doxorubicine › Ultrasound-mediated delivery of doxorubicin to...
questionsmedicales.fr › Eucaryotes › Animaux › Ultrasound-mediated delivery of doxorubicin to...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Ultrasound-mediated delivery of doxorubicin to...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Antigènes de différenciation › Antigènes de différenciation des lymphocytes T › Récepteur-1 de mort cellulaire programmée › Ultrasound-mediated delivery of doxorubicin to...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Ultrasound-mediated delivery of doxorubicin to...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Barrière hémato-encéphalique › Ultrasound-mediated delivery of doxorubicin to...
questionsmedicales.fr › Maladies du système nerveux › Tumeurs du système nerveux › Tumeurs du système nerveux central › Tumeurs du cerveau › Ultrasound-mediated delivery of doxorubicin to...
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questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Ultrasound-mediated delivery of doxorubicin to...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs du tissu nerveux › Tumeurs neuroectodermiques › Tumeurs neuroépitheliales › Gliome › Ultrasound-mediated delivery of doxorubicin to...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Ultrasound-mediated delivery of doxorubicin to...
questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Systèmes de délivrance de médicaments › Ultrasound-mediated delivery of doxorubicin to...
questionsmedicales.fr › Phénomènes physiques › Rayonnement › Rayonnement non ionisant › Son (physique) › Ondes ultrasonores › Ultrasound-mediated delivery of doxorubicin to...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs du tissu nerveux › Tumeurs neuroectodermiques › Tumeurs neuroépitheliales › Gliome › Astrocytome › Glioblastome › Ultrasound-mediated delivery of doxorubicin to...
questionsmedicales.fr › Cellules › Névroglie › Microglie › Ultrasound-mediated delivery of doxorubicin to...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Ultrasound-mediated delivery of doxorubicin to...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps monoclonaux › Anticorps monoclonaux humanisés › Ultrasound-mediated delivery of doxorubicin to...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antinéoplasiques › Antinéoplasiques immunologiques › Inhibiteurs de points de contrôle immunitaires › Ultrasound-mediated delivery of doxorubicin to...
questionsmedicales.fr › Technologie, industrie et agriculture › Produits manufacturés › Matériaux biomédicaux et dentaires › Polymères › Polyéthylène glycols › Ultrasound-mediated delivery of doxorubicin to...