Iron oxide nanoparticles-loaded hyaluronic acid nanogels for MRI-aided Alzheimer's disease theranostics

Abstract

Despite eye-opening advances in developing novel therapeutics for hard-to-treat diseases, treatment of Alzheimer's disease (AD) is still known as the challenge of generations. By the way, scrutinizing and shedding light on a major cause of AD, i.e., fibrillation of β amyloid (Aβ) peptides, have paved the way to find an effective therapy for this life-threatening disease in the foreseeable future. In this study, we endeavored to push forward with research on AD therapy, even as much as an inch, by fabricating and evaluating a theranostic system based on iron oxide nanoparticles-loaded hyaluronic acid nanogels (Fe 3 O 4 -HyA NGs). Fe 3 O 4 nanoparticles were fabricated via a facile co-precipitation method and were loaded in HyA NGs in situ by formation of NGs using a thiolated HyA (HyA-SH) precursor. Standard structural analysis was performed on Fe 3 O 4 -HyA NGs, and the results revealed the NGs were negatively charged, which led to relatively poor adsorption of plasma proteins, and sized at the range of 120–150 nm. Also, Fe 3 O 4 -HyA NGs showed a superparamagnetic property with a magnetic saturation of about 62.8 emu/g indicating the successful loading of Fe 3 O 4 nanoparticles. Besides, findings of the cytotoxicity analysis could primarily show the NGs did not pose a noticeable risk to normal astrocyte cells (i.e., 96.7% cell viability at 100 µg/ml after 48 h treatment). Moreover, in vitro magnetic resonance imaging (MRI) analysis could reveal the noticeable potential ability of the Fe 3 O 4 -HyA NGs to generate negative contrast by reducing both T2-weighted and T2*-weighted MR signal intensities with a relaxation rate (r 2 ) of about 120.87 (1/mM.sec). Finally, Fe 3 O 4 -HyA NGs exhibited a potential ability to impede Aβ aggregation by around 44% at 10 µM; also, they could induce disaggregation of Aβ fibrils by about 13% at 10 µM. Hence, Fe 3 O 4 -HyA NGs could be a promising choice for AD theranostics and could be further scrutinized in vitro and in vivo .