Arginine-Modified Polymers Facilitate Poly (Lactide-Co-Glycolide)-Based Nanoparticle Gene Delivery to Primary Human Astrocytes.

Astrocyte dysfunction is a hallmark of central nervous system injury or infection. As a primary contributor to neurodegeneration, astrocytes are an ideal therapeutic target to combat neurodegenerative conditions. Gene therapy has arisen as an innovative technique that provides excellent prospect for disease intervention. Poly (lactide-co-glycolide) (PLGA) and polyethylenimine (PEI) are polymeric nanoparticles commonly used in gene delivery, each manifesting their own set of advantages and disadvantages. As a clinically approved polymer by the Federal Drug Administration, well characterized for its biodegradability and biocompatibility, PLGA-based nanoparticles (PLGA-NPs) are appealing for translational gene delivery systems. However, our investigations revealed PLGA-NPs were ineffective at facilitating exogenous gene expression in primary human astrocytes, despite their success in other cell lines. Furthermore, PEI polymers illustrate high delivery efficiency but induce cytotoxicity. The purpose of this study is to develop viable and biocompatible NPsystem for astrocyte-targeted gene therapy. Successful gene expression by PLGA-NPs alone or in combination with arginine-modified PEI polymers (A Confocal imaging of YOYO-labeled pDNA confirmed PLGA-NPs delivered pDNA to the cytoplasm in a dose and time-dependent manner. However, co-staining revealed pDNA delivered by PLGA-NPs did not localize to the nucleus. The addition of A By co-transfecting two polymeric NPs, we developed an improved system for gene delivery and expression in primary human astrocytes. These findings provide a basis for a biocompatible and clinically translatable method to regulate astrocyte function during neurodegenerative diseases and disorders.

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© 2020 Proulx et al.

Déclaration de conflit d'intérêts

CJ’s current affiliation is Department of Neurology and Neurotherapeutics at the University of Texas Southwestern Medical Center, Dallas, TX, USA. SV’s current affiliation is Central Research Facility, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, India. MS’s current affiliation is the Department of Biomaterial Science and Technology, Sree Chitra Tirunal Institute for Medical Science and Technology, Trivandrum, Kerala, India. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.