Delivery of extracellular vesicles loaded with immune checkpoint inhibitors for immunotherapeutic management of glioma.

Autor:	Lin SW; School of Pharmacy, College of Medicine, National Cheng Kung University, No. 1, University Road, Tainan City, 701, Taiwan., Yu CP; School of Pharmacy, College of Medicine, National Cheng Kung University, No. 1, University Road, Tainan City, 701, Taiwan., Tsai JC; School of Pharmacy, College of Medicine, National Cheng Kung University, No. 1, University Road, Tainan City, 701, Taiwan., Shyong YJ; School of Pharmacy, College of Medicine, National Cheng Kung University, No. 1, University Road, Tainan City, 701, Taiwan.
Jazyk:	angličtina
Zdroj:	Materials today. Bio [Mater Today Bio] 2024 Sep 14; Vol. 28, pp. 101244. Date of Electronic Publication: 2024 Sep 14 (Print Publication: 2024).
DOI:	10.1016/j.mtbio.2024.101244
Abstrakt:	Glioma is a common primary malignant brain tumor with low survival rate. Immunotherapy with immune checkpoints inhibitors (ICI) can be a choice for glioma management, and extracellular vesicles (EVs) are recognized as a potential drug delivery system for various disease management due to their enhanced barrier permeation ability and immunomodulatory effect. The aim of this study is to develop ICI-loaded EVs (ICI/EV) that have sufficient efficacy in managing glioma. Calcium phosphate particles (CaP) were used to stimulate the secretion of EVs from murine macrophage cells. CaP conditioning of cells showed an enhanced amount of EVs secretion and macrophage polarization toward a proinflammatory phenotype. The CaP-induced EVs were shown to polarize macrophages into proinflammatory phenotype in vitro , as correlated with the conditioning method. ICI/EVs were successfully prepared with high loading efficiency using the sonication method. The EVs can be distributed throughout the entire brain upon intranasal administration and facilitate ICIs distribution into glioma lesion. Combinatory treatment with ICI/EVs showed benefit in glioma-bearing mice by reducing their tumor volume and prolonging their survival. Cytotoxic T cell infiltration, polarization of tumor-associated macrophage, and lower tumor proliferation were observed in ICI/EVs-treated mice. The developed ICI/EVs showed promise in immunotherapeutic management of glioma. Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Yan-Jye Shyong reports financial support was provided by 10.13039/100020595National Science and Technology Council. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2024 The Authors.)
Databáze:	MEDLINE
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