Dense hydroxyl polyethylene glycol dendrimer targets activated glia in multiple CNS disorders.

Autor:	Sharma A; Center for Nanomedicine, Department of Ophthalmology, Wilmer Eye Institute Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA., Sharma R; Center for Nanomedicine, Department of Ophthalmology, Wilmer Eye Institute Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA., Zhang Z; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Liaw K; Center for Nanomedicine, Department of Ophthalmology, Wilmer Eye Institute Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore MD 21218, USA., Kambhampati SP; Center for Nanomedicine, Department of Ophthalmology, Wilmer Eye Institute Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA., Porterfield JE; Center for Nanomedicine, Department of Ophthalmology, Wilmer Eye Institute Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore MD 21218, USA., Lin KC; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore MD 21218, USA., DeRidder LB; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore MD 21218, USA., Kannan S; Center for Nanomedicine, Department of Ophthalmology, Wilmer Eye Institute Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Hugo W. Moser Research Institute at Kennedy Krieger Inc., Baltimore, MD 21205, USA., Kannan RM; Center for Nanomedicine, Department of Ophthalmology, Wilmer Eye Institute Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore MD 21218, USA.; Hugo W. Moser Research Institute at Kennedy Krieger Inc., Baltimore, MD 21205, USA.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2020 Jan 22; Vol. 6 (4), pp. eaay8514. Date of Electronic Publication: 2020 Jan 22 (Print Publication: 2020).
DOI:	10.1126/sciadv.aay8514
Abstrakt:	Poor transport of neuropharmaceutics through central nervous system (CNS) barriers limits the development of effective treatments for CNS disorders. We present the facile synthesis of a novel neuroinflammation-targeting polyethylene glycol-based dendrimer (PEGOL-60) using an efficient click chemistry approach. PEGOL-60 reduces synthetic burden by achieving high hydroxyl surface density at low generation, which plays a key role in brain penetration and glia targeting of dendrimers in CNS disorders. Systemically administered PEGOL-60 crosses impaired CNS barriers and specifically targets activated microglia/macrophages at the injured site in diverse animal models for cerebral palsy, glioblastoma, and age-related macular degeneration, demonstrating its potential to overcome impaired blood-brain, blood-tumor-brain, and blood-retinal barriers and target key cells in the CNS. PEGOL-60 also exhibits powerful intrinsic anti-oxidant and anti-inflammatory effects in inflamed microglia in vitro. Therefore, PEGOL-60 is an effective vehicle to specifically deliver therapies to sites of CNS injury for enhanced therapeutic outcomes in a range of neuroinflammatory diseases. (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)
Databáze:	MEDLINE
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