Issue 20, 2023

Prodrug-loaded semiconducting polymer hydrogels for deep-tissue sono-immunotherapy of orthotopic glioblastoma

Abstract

Although immunotherapy has achieved great success in the treatment of a variety of tumors, its efficacy for glioblastoma (GBM) is still limited. Both the immunosuppressive tumor microenvironment (TME) and poor penetration of immunotherapeutic agents into tumors contributed to the poor anti-glioma immunity. Herein, we develop an injectable prodrug-loaded hydrogel delivery system with sono-activatable properties for sonodynamic therapy (SDT)-triggered immunomodulation for GBM treatment. The prodrug alginate hydrogels (APN), which contain semiconducting polymer nanoparticles (SPNs) and the NLG919 prodrug linked by singlet oxygen (1O2)-cleavable linkers, are in situ formed via coordination of alginate solution with Ca2+ in the TME. SPNs serve as sonosensitizers to produce 1O2 upon ultrasound (US) irradiation for SDT. The generated 1O2 not only induce immunogenic cell death, but also break 1O2-cleavable linkers to precisely activate the NLG919 prodrug. Antitumor immunity is significantly amplified due to the reversal of immunosuppression mediated by indolamine 2,3-dioxygenase-dependent tryptophan metabolism. This smart prodrug hydrogel platform potently inhibits tumor growth in orthotopic glioma-bearing mice. Collectively, this work provides a sono-activatable hydrogel platform for precise sono-immunotherapy against GBM.

Graphical abstract: Prodrug-loaded semiconducting polymer hydrogels for deep-tissue sono-immunotherapy of orthotopic glioblastoma

Supplementary files

Article information

Article type
Paper
Submitted
08 Кві 2023
Accepted
10 Сер 2023
First published
15 Сер 2023

Biomater. Sci., 2023,11, 6823-6833

Prodrug-loaded semiconducting polymer hydrogels for deep-tissue sono-immunotherapy of orthotopic glioblastoma

L. Zhu, X. Wang, M. Ding, N. Yu, Y. Zhang, H. Wu, Q. Zhang, J. Liu and J. Li, Biomater. Sci., 2023, 11, 6823 DOI: 10.1039/D3BM00585B

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