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Article

Nanotherapeutic Modulation of Human Neural Cells and Glioblastoma in Organoids and Monocultures

1
Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir-William-Osler, Montreal, QC H3G 1Y6, Canada
2
The Neuro’s Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada
3
Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustraße 3, 14195 Berlin, Germany
*
Author to whom correspondence should be addressed.
Cells 2020, 9(11), 2434; https://doi.org/10.3390/cells9112434
Received: 23 August 2020 / Revised: 4 November 2020 / Accepted: 5 November 2020 / Published: 7 November 2020
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Cancers: Glioblastoma)
Inflammatory processes in the brain are orchestrated by microglia and astrocytes in response to activators such as pathogen-associated molecular patterns, danger-associated molecular patterns and some nanostructures. Microglia are the primary immune responders in the brain and initiate responses amplified by astrocytes through intercellular signaling. Intercellular communication between neural cells can be studied in cerebral organoids, co-cultures or in vivo. We used human cerebral organoids and glioblastoma co-cultures to study glia modulation by dendritic polyglycerol sulfate (dPGS). dPGS is an extensively studied nanostructure with inherent anti-inflammatory properties. Under inflammatory conditions, lipocalin-2 levels in astrocytes are markedly increased and indirectly enhanced by soluble factors released from hyperactive microglia. dPGS is an effective anti-inflammatory modulator of these markers. Our results show that dPGS can enter neural cells in cerebral organoids and glial cells in monocultures in a time-dependent manner. dPGS markedly reduces lipocalin-2 abundance in the neural cells. Glioblastoma tumoroids of astrocytic origin respond to activated microglia with enhanced invasiveness, whereas conditioned media from dPGS-treated microglia reduce tumoroid invasiveness. Considering that many nanostructures have only been tested in cancer cells and rodent models, experiments in human 3D cerebral organoids and co-cultures are complementary in vitro models to evaluate nanotherapeutics in the pre-clinical setting. Thoroughly characterized organoids and standardized procedures for their preparation are prerequisites to gain information of translational value in nanomedicine. This study provides data for a well-characterized dendrimer (dPGS) that modulates the activation state of human microglia implicated in brain tumor invasiveness. View Full-Text
Keywords: cerebral organoids; nanomedicines; astrocytes; microglia; glioblastoma; lipocalin-2; inflammation cerebral organoids; nanomedicines; astrocytes; microglia; glioblastoma; lipocalin-2; inflammation
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MDPI and ACS Style

Zhang, I.; Lépine, P.; Han, C.; Lacalle-Aurioles, M.; Chen, C.X.-Q.; Haag, R.; Durcan, T.M.; Maysinger, D. Nanotherapeutic Modulation of Human Neural Cells and Glioblastoma in Organoids and Monocultures. Cells 2020, 9, 2434. https://doi.org/10.3390/cells9112434

AMA Style

Zhang I, Lépine P, Han C, Lacalle-Aurioles M, Chen CX-Q, Haag R, Durcan TM, Maysinger D. Nanotherapeutic Modulation of Human Neural Cells and Glioblastoma in Organoids and Monocultures. Cells. 2020; 9(11):2434. https://doi.org/10.3390/cells9112434

Chicago/Turabian Style

Zhang, Issan; Lépine, Paula; Han, Chanshuai; Lacalle-Aurioles, María; Chen, Carol X.-Q.; Haag, Rainer; Durcan, Thomas M.; Maysinger, Dusica. 2020. "Nanotherapeutic Modulation of Human Neural Cells and Glioblastoma in Organoids and Monocultures" Cells 9, no. 11: 2434. https://doi.org/10.3390/cells9112434

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