Polymerization of amyloid-β peptide （Aβ） into amyloid fibrils is a critical step in the pathogenesis of Alzheimer＇s disease （AD）. Inhibition of Aβ aggregation and destabilization of preformed Aβ fibrils have promising effects against AD and have been used in clinic trials. Herein, we demonstrate, for the first time, the application of WS2 nanosheets, to not only effectively inhibit Aβ aggregation, but also dissociate preformed Aβ aggregates upon near infrared （NIR） irradiation. Additionally, the biocompatible WS2 nanosheets possess the ability to cross the blood-brain barrier （BBB） to overcome the limitations of most previously reported Aβ inhibitors. Through van der Waals and electrostatic interactions between Aβ40 and WS2, Aβ40 monomers can be selectively adsorbed on the surface of the nanosheet to inhibit the Aβ40 aggregation process. Intriguingly, the unique high NIR absorption property of WS2 enables amyloid aggregates to be dissolved upon NIR irradiation. These results will promote biological applications of WS2 and provide new insight into the design of multifunctional nanomaterials for AD treatment.
Meng Li Andong Zhao Kai Dong Wen Li Jinsong Ren Xiaogang Qu
Metal ions are involved in Aβ aggregate deposition and neurotoxicity via various processes, including acceleration of Aβ aggregation, disruption of normal metal homeostasis, and formation of reactive oxygen species （ROS）. Although metal chelation is a promising therapeutic strategy for Alzheimer＇s disease （AD）, the widespread use of chelation therapy faces a significant problem; namely, it is difficult to differentiate toxic metals associated with Aβ plaques from those required by normal metal homeostasis. Furthermore, the multifactorial nature of AD and the current lack of an accepted unitary theory to account for AD neurodegeneration also restrict AD treatment through a single therapeutic strategy. This paper presents a novel bifunctional platform by integrating nonpharmacological and pharmacological cues into one system for AD treatment. This electrically responsive drug release platform, based on conducting polymer polypyrrole （PPy） incorporated with graphene-mesoporous silica nanohybrids （GSN） nanoreserviors, could realize on-demand controlled drug delivery with spatial and temporal control. Electrochemical stimulation can treat peripheral nerve injury （PNI） to stimulate neurite outgrowth. This novel system can also effectively inhibit Aβ aggregate formation, decrease cellular ROS, and protect cells from Aβ-related toxicity. The purpose of this research is to promote the design of noninvasive remote-controlled multifunctional systems for AD treatment.
Li WuJiasi WangNan GaoJinsong RenAndong ZhaoXiaogang Qu
We report a new strategy for improving the efficiency of non-specific amyloidosis therapeutic drugs by coating amyloid-responsive lipid bilayers. The approach had drawn inspiration from amyloid oligomer-mediated cell membrane disruption in the pathogenesis of amyloidosis. A graphene-mesoporous silica hybrid （GMS）-supported lipid bilayer （GMS-Lip） system was used as a drug carrier, Drugs were well confined inside the nanocarrier until encountering amyloid oligomers, which could pierce the lipid bilayer coat and cause drug release. To ensure release efficiency, use of a near-infrared （NIR） laser was also introduced to facilitate drug release, taking advantage of the photothermal effect of GMS and thermal sensitivity of lipid bilayers. To facilitate tracking, fluorescent dyes were co-loaded with drugs within GMS-Lip and the NIR laser was used once the oligomer-triggered release had been signaled. Because of the spatially and temporally controllable property of light, the NIR-assisted release could be easily and selectively activated locally by tracking the fluorescence signal. Our design is based on arnyloidosis pathogenesis, the cytotoxic amyloid oligomer self-triggered release via cell membrane disruption, for the controlled release of drug molecules. The results may shed light on the development of pathogenesis- inspired drug delivery systems,
Semiconductor nanomaterials with photocatalytic activity have potential for many applications. An effective way of promoting photocatalytic activity is depositing noble metal nanoparticles （NPs） on a semiconductor, since the noble metal NPs act as excellent electron acceptors which inhibit the quick recombination of the photoexcited electron-hole pairs and thereby enhance the generation of reactive oxygen species （ROS）. Herein, a highly effective platform, graphitic carbon nitride （g-C3N4） nanosheets with embedded Ag nanopartides （Ag/g-C3N4）, was synthesized by a facile route. Under visible light irradiation, the ROS production of Ag/g-C3N4 nanohybrids was greatly improved compared with pristine g-C3N4 nanosheets, and moreover, the nanohybrids showed enhanced antibacterial efficacy and ability to disperse bacterial biofilms. We demonstrate for the first time that the Ag/g-C3N4 nanohybrids are efficient bactericidal agents under visible light irradiation, and can also provide a new way for biofilm elimination. The enhanced antibacterial properties and biofilm-disrupting ability of Ag/g-C3N4 nanohybrids may offer many biomedical applications.
