Development of GG-MA:MnO2 nanoreactors for MRI Imaging

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease which is not fully understood. Previous studies have shown evidences that oxidative stress can be involved in motor neuron degeneration in ALS, having the possibility of becoming a therapeutic target [1,4]. Manganese Enhanced Magnetic Resonance Imaging (MEMRI) has been used to study functionality, anatomy and neural connection within the nervous system and it can also be used to guide intrathecal drug/cell delivery [1]. Manganese ions (Mn²⁺) are important for brain health, can enter excitable cells and be transported along axons and across synapses. Additionally, they can be used as contrast agent for long-term T1-weighted imaging [1]. Studies have shown that manganese dioxide (MnO₂) nanoparticles are able to scavenge Reactive Oxygen Species (ROS), via decomposition of hydrogen peroxide in water, oxygen and Mn²⁺ [2]. Thus, we intend to develop MnO₂ nano/microreactors that can be delivered and guided by MRI, thus regulating cell death apoptotic mechanisms and modulating inflammation in tissues. These MnO₂ nanoparticles are toxic at high dosages and induce adverse effects in cells [2]. Thus, the nanoparticles will be blended with a methacrylated gellan-gum (GG-MA) based matrix. GG-MA is an anionic microbial polysaccharide that was chosen due to its biocompatibility, biodegradability, easy functionalization and similarity with the extracellular matrix, as well as due to its high affinity with Mn²⁺ ions [3]. GG-MA was obtained as previously described [3], and chemically characterized by FTIR and ¹H-NMR. As a source of Mn²⁺, we intend to compare the activity of MnO₂ nanoparticles synthetized according to a previously published protocol and commercially available ones. Rheology, stability, permeability and morphology were evaluated and further studies considering cell viability and ROS scavenging ability will be pursued.