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

Anjali Sharma, Rishi Sharma, Zhi Zhang, Kevin Liaw, Siva P. Kambhampati, Joshua E. Porterfield, Ku Chien Lin, Louis B. DeRidder, Sujatha Kannan, Rangaramanujam M. Kannan

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbereaay8514
JournalScience Advances
Volume6
Issue number4
DOIs
StatePublished - Jan 22 2020

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