The progression of Alzheimer’s disease (AD) is characterized with the deposition and aggregation of β-amyloid (Aβ). Visualizing Aβ aggregates at high spatial resolution is beneficial for AD diagnosis and treatment. Herein, we designed a new molecule by conjugating corannulene (Cor) with rhodamine B isothiocyanate (Rhb), namely Cor-Rhb, for the nanoscopic imaging and modulating Aβ peptide fibrillation. The low duty cycle, high photon output and sufficient switching cycles enable Cor-Rhb suitable for localization-based nanoscopic fluorescence imaging. We find that Cor-Rhb can inhibit Aβ peptides fibrillization and interact directly with mature fibrils, triggering their disaggregation under light illumination. Noticeably reduced Aβ-mediated cytotoxicity after the addition of Cor-Rhb is also confirmed. These explorations suggest that Cor-Rhb displays great potential as a multifunctional therapeutic agent against amyloid-related diseases, and may largely facilitate a variety of super-resolution based biological applications.

Redox-responsive polymer-drug conjugate micelles are excellent nanoscale vehicles for self-immolative intracellular drug delivery. To covalently connect the polymer and drug, disulfide-bearing linkers, such as 3, 3'-dithiodipropionic acid (DDPA) and 4, 4'-dithiodibutyric acid (DDBA), are used. In this paper, we report the influence of linker length on the therapeutic outcome of redox-sensitive conjugate micelles. Curcumin was selected as the model drug and it was conjugated to a multivalent methoxy poly(ethylene glycol)-polylysine copolymer with DDPA or DDBA as the linker. The obtained two polymer-curcumin conjugates were amphiphilic and could self-assemble into micelles that have a hydrodynamic diameter less than 100 nm. The loading of curcumin in both micelles was above 20% (w/w). Irrespective of the linker type, micelle disassembly was observed due to the collapse of the disulfide bond in a reducing environment. However, the rate of curcumin release was much faster with the DDBA linker than with the DDPA linker as the side product was a 5-membered ring with a low ring strain. The linker length-induced variation of curcumin release kinetics caused a significant difference in the intracellular drug concentration and a higher cytotoxicity was witnessed in three model cell lines (HeLa, PC3, and 4T1) for the micelles with a DDBA linker compared to those containing a DDPA linker. As expected, this phenomenon was also observed in HeLa tumor-bearing nude mice in vivo. The current work highlights the significance of linker length in engineering redox-responsive on-demand delivery systems.