STING agonist-loaded, CD47/PD-L1-targeting nanoparticles potentiate antitumor immunity and radiotherapy for glioblastoma

Peng Zhang (), Aida Rashidi, Junfei Zhao, Caylee Silvers, Hanxiang Wang, Brandyn Castro, Abby Ellingwood, Yu Han, Aurora Lopez-Rosas, Markella Zannikou, Crismita Dmello, Rebecca Levine, Ting Xiao, Alex Cordero, Adam M. Sonabend, Irina V. Balyasnikova, Catalina Lee-Chang, Jason Miska () and Maciej S. Lesniak ()
Additional contact information
Peng Zhang: Northwestern University Feinberg School of Medicine
Aida Rashidi: Northwestern University Feinberg School of Medicine
Junfei Zhao: Columbia University
Caylee Silvers: Northwestern University Feinberg School of Medicine
Hanxiang Wang: Northwestern University Feinberg School of Medicine
Brandyn Castro: Northwestern University Feinberg School of Medicine
Abby Ellingwood: Northwestern University Feinberg School of Medicine
Yu Han: Northwestern University Feinberg School of Medicine
Aurora Lopez-Rosas: Northwestern University Feinberg School of Medicine
Markella Zannikou: Northwestern University Feinberg School of Medicine
Crismita Dmello: Northwestern University Feinberg School of Medicine
Rebecca Levine: Northwestern University Feinberg School of Medicine
Ting Xiao: Northwestern University Feinberg School of Medicine
Alex Cordero: Northwestern University Feinberg School of Medicine
Adam M. Sonabend: Northwestern University Feinberg School of Medicine
Irina V. Balyasnikova: Northwestern University Feinberg School of Medicine
Catalina Lee-Chang: Northwestern University Feinberg School of Medicine
Jason Miska: Northwestern University Feinberg School of Medicine
Maciej S. Lesniak: Northwestern University Feinberg School of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-19

Abstract: Abstract As a key component of the standard of care for glioblastoma, radiotherapy induces several immune resistance mechanisms, such as upregulation of CD47 and PD-L1. Here, leveraging these radiotherapy-elicited processes, we generate a bridging-lipid nanoparticle (B-LNP) that engages tumor-associated myeloid cells (TAMCs) to glioblastoma cells via anti-CD47/PD-L1 dual ligation. We show that the engager B-LNPs block CD47 and PD-L1 and promote TAMC phagocytic activity. To enhance subsequent T cell recruitment and antitumor responses after tumor engulfment, the B-LNP was encapsulated with diABZI, a non-nucleotidyl agonist for stimulator of interferon genes. In vivo treatment with diABZI-loaded B-LNPs induced a transcriptomic and metabolic switch in TAMCs, turning these immunosuppressive cells into antitumor effectors, which induced T cell infiltration and activation in brain tumors. In preclinical murine models, B-LNP/diABZI administration synergized with radiotherapy to promote brain tumor regression and induce immunological memory against glioma. In summary, our study describes a nanotechnology-based approach that hijacks irradiation-triggered immune checkpoint molecules to boost potent and long-lasting antitumor immunity against glioblastoma.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/s41467-023-37328-9 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:14:y:2023:i:1:d:10.1038_s41467-023-37328-9

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

DOI: 10.1038/s41467-023-37328-9

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 ().