Detection of ß-Amyloid by Sialic Acid Coated Bovine Serum Albumin Magnetic Nanoparticles in a Mouse Model of Alzheimer's Disease.

The accumulation and formation of ß-amyloid (Aß) plaques in the brain are distinctive pathological hallmarks of Alzheimer's disease (AD). Designing nanoparticle (NP) contrast agents capable of binding with Aß highly selectively can potentially facilitate early detection of AD. However, a significant obstacle is the blood brain barrier (BBB), which can preclude the entrance of NPs into the brain for Aß binding. In this work, bovine serum albumin (BSA) coated NPs are decorated with sialic acid (NP-BSAx -Sia) to overcome the challenges in Aß imaging in vivo. The NP-BSAx -Sia is biocompatible with high magnetic relaxivities, suggesting that they are suitable contrast agents for magnetic resonance imaging (MRI). The NP-BSAx -Sia binds with Aß in a sialic acid dependent manner with high selectivities toward Aß deposited on brains and cross the BBB in an in vitro model. The abilities of these NPs to detect Aß in vivo in human AD transgenic mice by MRI are evaluated without the need to coinject mannitol to increase BBB permeability. T2 *-weighted MRI shows that Aß plaques in mouse brains can be detected as aided by NP-BSAx -Sia, which is confirmed by histological analysis. Thus, NP-BSAx -Sia is a promising new tool for noninvasive in vivo detection of Aß plaques.

Lipoic acid glyco-conjugates, a new class of agents for controlling nonspecific adsorption of blood serum at biointerfaces for biosensor and biomedical applications.

The carbohydrate-derived lipoic acid derivatives were studied as protein and cell resistant biomaterials. Six types of carbohydrates were examined for their abilities to reduce nonspecific adsorption of human serum and Hela cell using quartz crystal microbalance. Our data suggested that the structures of carbohydrates play an important role in resisting nonspecific binding. Specifically, the resistance was found to increase in the order lipoic fucose < lipoic mannose < lipoic N-acetyl glucosamine < lipoic glucose < lipoic sialic acid < lipoic galactose, where lipoic galactose derivative resisted most nonspecific adsorption. Furthermore, the combination of lipoic galactose and BSA was the most effective in reducing the adsorption of even undiluted human serum and the attachment of Hela cells while allowing specific binding. Several control experiments have demonstrated that the resistant-ability of mixed lipoic galactose and BSA was comparable to the best known system for decreasing nonspecific adsorption.

Heparin nanoparticles for ß amyloid binding and mitigation of ß amyloid associated cytotoxicity.

Accumulation of ß amyloid (Aß) in the brain is believed to play a key role in the pathology of Alzheimer's disease. Glycosaminoglycans on surface of neuronal cells can serve as nucleation sites to promote plaque formation on cell surface. To mimic this process, magnetic nanoparticles coated with heparin have been synthesized. The heparin nanoparticles were demonstrated to bind with Aß through a variety of techniques including enzyme-linked immunosorbent assay, gel electrophoresis, and thioflavin T assay. The nanoparticle exhibited little toxicity to neuronal cells and at the same time can effectively protect them from Aß induced cytotoxicity. These results suggest that heparin nanoparticles can be a very useful tool for Aß studies.

Glyconanoparticle aided detection of ß-amyloid by magnetic resonance imaging and attenuation of ß-amyloid induced cytotoxicity.

The development of a noninvasive method for the detection of Alzheimer's disease is of high current interest, which can be critical in early diagnosis and in guiding treatment of the disease. The aggregates of ß-amyloid are a pathological hallmark of Alzheimer's disease. Carbohydrates such as gangliosides have been shown to play significant roles in initiation of amyloid aggregation. Herein, we report a biomimetic approach using superparamagnetic iron oxide glyconanoparticles to detect ß-amyloid. The bindings of ß-amyloid by the glyconanoparticles were demonstrated through several techniques including enzyme linked immunosorbent assay, gel electrophoresis, tyrosine fluorescence assay, and transmission electron microscopy. The superparamagnetic nature of the nanoparticles allowed easy detection of ß-amyloid both in vitro and ex vivo by magnetic resonance imaging. Furthermore, the glyconanoparticles not only were nontoxic to SH-SY5Y neuroblastoma cells but also greatly reduced ß-amyloid induced cytotoxicity to cells, highlighting the potential of these nanoparticles for detection and imaging of ß-amyloid.