Lipid–polymer hybrid nanoparticles loaded with N-acetylcysteine for the modulation of neuroinflammatory biomarkers in human iPSC-derived PSEN2 (N141I) astrocytes as a model of Alzheimer's disease†
Alondra Vargas-Barona, Johanna Bernáldez-Sarabia and Ana B. Castro-Ceseña
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引用次数: 0
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive impairment associated with the accumulation of beta-amyloid protein (Aβ). Aβ activates glial cells in the brain, increasing the secretion of proinflammatory cytokines, which leads to neuroinflammation and neuronal death. Currently, there are no effective treatments that cure or stop its progression; therefore, AD is considered a global health priority. The main limitations are the low drug bioavailability and impermeability of the blood–brain barrier (BBB). Fortunately, nanomedicine has emerged as a promising field for the development of new nanosystems for the controlled and targeted delivery of drugs to the brain. Therefore, in this work, lipid–polymer hybrid nanoparticles (LPHNPs) conjugated with transferrin (Tf) to facilitate crossing the BBB and loaded with N-acetylcysteine (NAC) for its anti-inflammatory effect were synthesized, and their physicochemical characterization was carried out. Subsequently, an in vitro model involving human astrocytes derived from induced pluripotent stem cells (iPSC) from an AD-diagnosed patient was developed, which was brought to a reactive state by stimulation with lipopolysaccharides (LPSs). The cell culture was treated with either Tf-conjugated LPHNPs loaded with NAC (NAC-Tf-LPHNPs) at 0.25 mg mL−1, or free NAC at 5 mM. The results showed that NAC-Tf-LPHNPs favorably modulated the expression of proinflammatory genes such as interleukin-1β (IL-1β), amyloid precursor protein (APP) and glial fibrillary acidic protein (GFAP). In addition, they reduced the secretion of the proinflammatory cytokines interleukin 6 (IL-6), IL-1β and interferon-gamma (INF-γ). Results for both cases were compared to the group of cells that did not receive any treatment. In contrast, free NAC only had this effect on the expression of IL-1β and the secretion of the cytokines IL-6 and INF-γ. These results indicate the potential of NAC-Tf-LPHNPs for AD treatment.
期刊介绍:
Journal of Materials Chemistry A, B & C cover high quality studies across all fields of materials chemistry. The journals focus on those theoretical or experimental studies that report new understanding, applications, properties and synthesis of materials. Journal of Materials Chemistry A, B & C are separated by the intended application of the material studied. Broadly, applications in energy and sustainability are of interest to Journal of Materials Chemistry A, applications in biology and medicine are of interest to Journal of Materials Chemistry B, and applications in optical, magnetic and electronic devices are of interest to Journal of Materials Chemistry C.Journal of Materials Chemistry B is a Transformative Journal and Plan S compliant. Example topic areas within the scope of Journal of Materials Chemistry B are listed below. This list is neither exhaustive nor exclusive:
Antifouling coatings
Biocompatible materials
Bioelectronics
Bioimaging
Biomimetics
Biomineralisation
Bionics
Biosensors
Diagnostics
Drug delivery
Gene delivery
Immunobiology
Nanomedicine
Regenerative medicine & Tissue engineering
Scaffolds
Soft robotics
Stem cells
Therapeutic devices