Photodynamic therapy (PDT) has been explored as a therapeutic strategy to clear toxic amyloid aggregates involved in neurodegenerative disorders such as Alzheimer's disease. A major limitation of PDT is off-target oxidation, which can be lethal for the surrounding cells. We have shown that a novel class of oligo-pphenylene ethynylenes (OPEs) exhibit selective binding and fluorescence turn-on in the presence of prefibrillar and fibrillar aggregates of disease-relevant proteins such as amyloid-β (Aβ) and αsynuclein. Concomitant with fluorescence turn-on, OPE also photosensitizes singlet oxygen under illumination through the generation of a triplet state, pointing to the potential application of OPEs as photosensitizers in PDT. Herein, we investigated the photosensitizing activity of an anionic OPE for the photo-oxidation of Aβ fibrils and compared its efficacy to the well-known but nonselective photosensitizer methylene blue (MB). Our results show that, while MB photo-oxidized both monomeric and fibrillar conformers of Aβ40, OPE oxidized only Aβ40 fibrils, targeting two histidine residues on the fibril surface and a methionine residue located in the fibril core. Oxidized fibrils were shorter and more dispersed but retained the characteristic β-sheet rich fibrillar structure and the ability to seed further fibril growth. Importantly, the oxidized fibrils displayed low toxicity. We have thus discovered a class of novel theranostics for the simultaneous detection and oxidization of amyloid aggregates. Importantly, the selectivity of OPE's photosensitizing activity overcomes the limitation of off-target oxidation of traditional photosensitizers and represents an advancement of PDT as a viable strategy to treat neurodegenerative disorders.

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This research introduces the use of electrospray drying (ESD) using the electro-hydro dynamic atomization (EHDA) mechanism to produce dry nano-scale cellulose nanocrystal (CNC) powder from a 3 wt% aqueous suspension. The nano-scale CNC suspensions being mostly water are energy intensive to dry. Gas atomization in convection spray drying (SD) produces micron-scale CNC powder during dehydration. The ESD mechanism utilizes coulomb repulsion to overcome the suspension’s liquid surface tension and produces ultra-fine droplets. The droplets dehydrate after falling a fixed distance at atmospheric temperature and pressure, leaving nano-scale powder CNCs. Drying CNCs in suspension occurred after reducing the liquid’s surface tension by mixing 40% (wt) ethanol and 60 (wt) de-ionized (DI) water. The suspension feed rate was optimized at 6 µL min−1 and four syringes were employed to increase CNC powder production rates. Particle dimensions, observed by scanning electron microscopy (SEM) and measured by image analysis software, ranged from 40 to 1200 nm in length and 10–500 nm in width. Up to 80% of the sprayed CNCs in suspension were recovered from a parallel plate collector and contained ~ 5 wt% water content. Adding 0.5 wt% nano-scale powder CNCs in the poly-lactic acid (PLA) tensile strength by 10.3% and elastic modulus by 9.9%. The tensile yield strength and elastic modulus of nano-scale CNC/PLA composite specimens were 62.5 MPa and 3.66 GPa, respectively. For comparison, 0.5 wt% SD micron scale CNC/PLA composite only increased strength 5.1 and stiffness 1.3% at the same processing conditions. Graphical abstract

Amyloid protein aggregates are pathological hallmarks of neurodegenerative disorders such as Alzheimer's (AD) and Parkinson's (PD) diseases and are believed to be formed well before the onset of neurodegeneration and cognitive impairment. Monitoring the course of protein aggregation is thus vital to understanding and combating these diseases. We have recently demonstrated that a novel class of fluorescence sensors, oligomeric pphenylene ethynylene (PE)-based electrolytes (OPEs) selectively bind to and detect prefibrillar and fibrillar aggregates of AD-related amyloid-β (Aβ) peptides over monomeric Aβ. In this study, we investigated the binding between two OPEs, anionic OPE 1 2− and cationic OPE 2 4+ , and to two different β-sheet rich Aβ oligomers using classical all-atom molecular dynamics simulations. Our simulations have revealed a number of OPE binding sites on Aβ oligomer surfaces, and these sites feature hydrophobic amino acids as well as oppositely charged amino acids. Binding energy calculations show energetically favorable interactions between both anionic and cationic OPEs with Aβ oligomers. Moreover, OPEs bind as complexes as well as single molecules. Compared to free OPEs, Aβ protofibril bound OPEs show backbone planarization with restricted rotations and reduced hydration of the ethyl ester end groups. These characteristics, along with OPE complexation, align with known mechanisms of binding induced OPE fluorescence turn-on and spectral shifts from a quenched, unbound state in aqueous solutions. This study thus sheds light on the molecular-level details of OPE-Aβ protofibril interactions and provides a structural basis for fluorescence turn-on sensing modes of OPEs.