Sulfur Nanoparticles with Novel Morphologies Coupled with Brain-Targeting Peptides RVG as a New Type of Inhibitor Against Metal-Induced Aβ Aggregation

Functionalized nanomaterials, which have been applied widely to inhibit amyloid-β protein (Aβ) aggregation, show enormous potential in the field of prevention and treatment of Alzheimer’s disease (AD). A significant body of data has demonstrated that the morphology and size of nanomaterials have remarkable effects on their biological behaviors. In this work, we proposed and designed three kinds of brain-targeting sulfur nanoparticles ([email protected]@SNPs) with novel morphologies (volute-like, tadpole-like, and sphere-like) and investigated the effect of different [email protected]@SNPs on Aβ–Cu2+ complex aggregation and their corresponding neurotoxicity. Among them, the sphere-like nanoparticles ([email protected]@SS) exhibited the most effective inhibitory activity, due to their unique mini size effect, and they reduced 61.6% the Aβ–Cu2+ complex aggregation and increased 92.4% SH-SY5Y cell viability in a dose of 10 μg/mL. In vitro and in vivo, the abilities of different morphologies of [email protected]@SNPs to cross the blood–brain barrier (BBB) and target brain parenchymal cells were significantly different. Moreover, improvements in learning disability and cognitive loss were shown in the transgenic AD mice model using the Morris water maze test after multiple doses of [email protected]@SNPs treatment. In general, the purpose of this research is to develop a biological application of sulfur nanoparticles and to provide a novel functionalized nanomaterial to treat AD