Jing Sun,Wenjie Xie,Xufeng Zhu,Mengmeng Xu,Jie Liu
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 (RVG@Met@SNPs) with novel morphologies (volute-like, tadpole-like, and sphere-like) and investigated the effect of different RVG@Met@SNPs on Aβ–Cu2+ complex aggregation and their corresponding neurotoxicity. Among them, the sphere-like nanoparticles (RVG@Met@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 RVG@Met@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 RVG@Met@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.
Neuroblastoma accounts for 8–10% of malignancies in infants and children. It is urgent to develop an appropriate theranostic agent for effective diagnosis and therapy of neuroblastoma. Herein, we constructed RVG peptide and IRDye800-conjugated bovine serum albumin-coated triangular gadolinium oxide nanoplates (RVG&IRDye800-Gd 2 O 3 TNs) as a targeting MRI agent for the diagnosis of neuroblastoma preoperation and a fluorescence imaging agent for the guidance of the precise excision of the neuroblastoma in surgery. RVG&IRDye800-Gd 2 O 3 TNs have uniform edge length. The RVG&IRDye800-Gd 2 O 3 TNs show remarkably enhanced affinity to both mouse- and human-derived neuroblastoma cells compared with IRDye800-Gd 2 O 3 TNs (3.07-fold and 3.02-fold, respectively). Because of the increased accumulation in tumor cells, RVG&IRDye800-Gd 2 O 3 TNs exhibit signals threefold to fivefold higher than the surrounding normal tissues, which is propitious to the diagnosis of neuroblastoma preoperation and provides real-time visual guidance of the precise excision of the neuroblastoma. Most importantly, with the guidance of the fluorescence imaging agent, the survival rate increased from 0% to 80% 42 days after surgery compared with that in conventional surgery. These findings indicated that the RVG peptide combined with IRDye800-Gd 2 O 3 TNs has the potential to improve the diagnosis and treatment of patients with neuroblastoma. Statement of significance In this study, we prepared RVG peptide and IRDye800-conjugated bovine serum albumin-coated triangular gadolinium oxide nanoplates (RVG&IRDye800-Gd 2 O 3 TNs) as a targeting MRI agent for the diagnosis of neuroblastoma preoperation and a fluorescence imaging agent for the guidance of the precise excision of the neuroblastoma during surgery. Neuroblastoma was accurately located by MRI imaging, and the tumor margin could be real-time monitored through near-infrared fluorescence imaging. The RVG&IRDye800-Gd 2 O 3 TNs exhibit signals threefold to fivefold higher than those in the surrounding normal tissues, which is propitious to the diagnosis of the neuroblastoma preoperation and provides real-time visual guidance of the precise excision of the neuroblastoma. With the guidance of the fluorescence imaging agent in surgery, the survival rate increased from 0% to 80% 42 days after surgery compared with that in conventional surgery.
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