Near-Infrared Activated Black Phosphorus as a Nontoxic Photo-Oxidant for Alzheimer's Amyloid-ß Peptide.

The inhibition of amyloid-ß (Aß) aggregation by photo-oxygenation has become an effective way of treating Alzheimer's disease (AD). New near-infrared (NIR) activated treatment agents, which not only possess high photo-oxygenation efficiency, but also show low biotoxicity, are urgently needed. Herein, for the first time, it is demonstrated that NIR activated black phosphorus (BP) could serve as an effective nontoxic photo-oxidant for amyloid-ß peptide in vitro and in vivo. The nanoplatform BP@BTA (BTA: one of thioflavin-T derivatives) possesses high affinity to the Aß peptide due to specific amyloid selectivity of BTA. Importantly, under NIR light, BP@BTA can significantly generate a high quantum yield of singlet oxygen (1 O2 ) to oxygenate Aß, thereby resulting in inhibiting the aggregation and attenuating Aß-induced cytotoxicity. In addition, BP could finally degrade into nontoxic phosphate, which guarantees the biosafety. Using transgenic Caenorhabditis elegans CL2006 as AD model, the results demonstrate that the 1 O2 -generation system could dramatically promote life-span extension of CL2006 strain by decreasing the neurotoxicity of Aß.

Photo-induced inhibition of Alzheimer's ß-amyloid aggregation in vitro by rose bengal.

The abnormal aggregation of ß-amyloid (Aß) peptides in the brain is a major pathological hallmark of Alzheimer's disease (AD). The suppression (or alteration) of Aß aggregation is considered to be an attractive therapeutic intervention for treating AD. We report on visible light-induced inhibition of Aß aggregation by xanthene dyes, which are widely used as biomolecule tracers and imaging markers for live cells. Among many xanthene dyes, rose bengal (RB) under green LED illumination exhibited a much stronger inhibition effect upon photo-excitation on Aß aggregation than RB under dark conditions. We found that RB possesses high binding affinity to Aß; it exhibits a remarkable red shift and a strong enhancement of fluorescence emission in the presence of Aß. Photo-excited RB interfered with an early step in the pathway of Aß self-assembly and suppressed the conformational transition of Aß monomers into ß-sheet-rich structures. Photo-excited RB is not only effective in the inhibition of Aß aggregation, but also in the reduction of Aß-induced cytotoxicity.

Low energy laser light (632.8 nm) suppresses amyloid-ß peptide-induced oxidative and inflammatory responses in astrocytes.

Oxidative stress and inflammation are important processes in the progression of Alzheimer's disease (AD). Recent studies have implicated the role of amyloid ß-peptides (Aß) in mediating these processes. In astrocytes, oligomeric Aß induces the assembly of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complexes resulting in its activation to produce anionic superoxide. Aß also promotes production of pro-inflammatory factors in astrocytes. Since low energy laser has previously been reported to attenuate oxidative stress and inflammation in biological systems, the objective of this study was to examine whether this type of laser light was able to abrogate the oxidative and inflammatory responses induced by Aß. Primary rat astrocytes were exposed to Helium-Neon laser (λ=632.8 nm), followed by the treatment with oligomeric Aß. Primary rat astrocytes were used to measure Aß-induced production of superoxide anions using fluorescence microscopy of dihydroethidium (DHE), assembly of NADPH oxidase subunits by the colocalization between the cytosolic p47(phox) subunit and the membrane gp91(phox) subunit using fluorescent confocal microscopy, phosphorylation of cytosolic phospholipase A(2) cPLA(2) and expressions of pro-inflammatory factors including interleukin-1ß (IL-1ß) and inducible nitric-oxide synthase (iNOS) using Western blot Analysis. Our data showed that laser light at 632.8 nm suppressed Aß-induced superoxide production, colocalization between NADPH oxidase gp91(phox) and p47(phox) subunits, phosphorylation of cPLA(2,) and the expressions of IL-1ß and iNOS in primary astrocytes. We demonstrated for the first time that 632.8 nm laser was capable of suppressing cellular pathways of oxidative stress and inflammatory responses critical in the pathogenesis in AD. This study should prove to provide the groundwork for further investigations for the potential use of laser therapy as a treatment for AD.