Picomolar-sensitive ß-amyloid fibril fluorophores by tailoring the hydrophobicity of biannulated π-elongated dioxaborine-dyes.

The pathological origin of Alzheimer's disease (AD) is still shrouded in mystery, despite intensive worldwide research efforts. The selective visualization of ß-amyloid (Aß), the most abundant proteinaceous deposit in AD, is pivotal to reveal AD pathology. To date, several small-molecule fluorophores for Aß species have been developed, with increasing binding affinities. In the current work, two organic small-molecule dioxaborine-derived fluorophores were rationally designed through tailoring the hydrophobicity with the aim to enhance the binding affinity for Aß1-42 fibrils -while concurrently preventing poor aqueous solubility-via biannulate donor motifs in D-π-A dyes. An unprecedented sub-nanomolar affinity was found (K d = 0.62 ± 0.33 nM) and applied to super-sensitive and red-emissive fluorescent staining of amyloid plaques in cortical brain tissue ex vivo. These fluorophores expand the dioxaborine-curcumin-based family of Aß-sensitive fluorophores with a promising new imaging agent.

Nanoscale porous organic polymers for drug delivery and advanced cancer theranostics.

Finding a personalized nano theranostics solution, a nanomedicine for cancer diagnosis and therapy, is among the top challenges of current medicinal science. Porous organic polymers (POPs) are permanent porous organic materials prepared by linking relatively rigid multidimensional organic building blocks. POP nanoparticles have a remarkable advantage for cancer theranostics owing to their specific physicochemical characteristics such as high surface area, convincing pore size engineering, stimuli-responsive degradability, negligible toxicity, open covalent post-synthesis modification possibilities etc. POPs have crystalline and non-crystalline characteristics; crystalline POPs are popularly known as covalent organic frameworks (COFs), and have shown potential application across research areas in science. The early research and development on theranostics applications of nanoscale POPs has shown tremendous future potential for clinical translation. This tutorial review highlights the recently developed promising applications of nPOPs in drug loading, targeted delivery, endogenous and exogenous stimuli-responsive release, cancer imaging and combination therapy, regardless of their crystalline and poorly crystalline properties. The review will provide a platform for the future development and clinical translation of nPOPs by solving fundamental challenges of cancer nanomedicines in drug loading efficiency, size-optimization, biocompatibility, dispersibility and cell uptake ability.

Metabolic iron detection through divalent metal transporter 1 and ferroportin mediated cocktail fluorogenic probes.

A cocktail [1 + 2] dual-fluorescent probe system was developed to realize the real-time visualization of dynamic iron state changes between Fe2+ and Fe3+ at the cellular level and in multicellular organisms, providing insights into the effect of DMT1 and ferroportin on iron regulation.