Synthesis of carboxymethyl chitosan-coated magnetite nanoparticles and their protective effect against manganese ion-induced damage in human neuroblastoma SH-SY5Y cells

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Background:Excessive intake of manganese can accumulate in the body, causing damage to the nervous system and triggering a series of serious medical problems. Finding effective methods to remove excess manganese ions from the body is crucial for related diseases. It aimed to prepare carboxymethyl chitosan (CMCS)-coated magnetite nanoparticles (Fe3O4 NPs) (CMCS-Fe3O4 NPs) and investigate their effects on human neuroblastoma SH-SY5Y cells. Methods: Fe3O4 NPs were prepared using the co-precipitation method and coated with CMCS to obtain CMCS-Fe3O4 NPs. Simulated manganese ion wastewater solutions of different concentrations were prepared for adsorption experiments. SH-SY5Y cells were used to construct a nerve cell damage model, with cells grouped: blank group (BG), model group (MG), and intervention group (IG, treated with CMCS-Fe3O4 NPs solution). Multiplication activity, reactive oxygen species (ROS) content, apoptosis rate (AR), and transfer and attack capabilities were recorded. With increasing initial manganese ion concentration, the adsorption capacities of both CMCS-Fe3O4NPs and Fe3O4 NPs increased, with the former consistently exhibiting higher values (maximum experimental saturated adsorption capacity: 118.3 mg/g). The particle size of CMCS-Fe3O4 NPs (53–99 nm) was larger than that of Fe3O4 NPs (22–50 nm), but the uniformity of distribution did not improve. The zeta potential became more negative (−30.08 ± 0.08 mV), and superparamagnetism was retained (saturation magnetization: 65.2 emu/g). Compared with the BG group, the MG group showed reduced cell proliferation, increased apoptosis, decreased migration and invasion abilities, and a significant increase in ROS level to 318.52 ± 11.36 (P < 0.01). In contrast, the IG group exhibited increased proliferation, decreased apoptosis, and enhanced migration and invasion capacities compared to the MG group (P < 0.05), along with a reduction in ROS level to 182.47 ± 7.93 (P < 0.01). CMCS-Fe3O4 NPs exhibit excellent adsorption capacity for manganese ions and alleviate manganese-induced damage in SH-SY5Y cells through dual mechanisms of adsorbing manganese ions and scavenging ROS, demonstrating potential application value in the prevention and treatment of manganese-related neurotoxic diseases. The innovation of this study lies in the first application of CMCS-Fe3O4 NPs in repairing manganese-induced neuronal cell injury. By precisely optimizing the mass ratio of CMCS to Fe3O4 NPs and the coating process parameters, the composite material retains the superparamagnetism of Fe3O4 NPs while significantly enhancing the adsorption capacity for manganese ions and maintaining excellent adsorption stability within the physiological pH range. This work provides a novel functional material and experimental basis for the targeted treatment of manganese poisoning.

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