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The presence of protein aggregates in numerous human diseases underscores the significance of detecting these aggregates to comprehend disease mechanisms and develop novel therapeutic approaches for combating these disorders. Despite the development of various biosensors and fluorescent probes that selectively target amyloid fibers or amorphous aggregates, there is still a lack of tools capable of simultaneously detecting both types of aggregates. Herein, we demonstrate the quantitative discernment of amorphous aggregates by QM‐FN‐SO3, an aggregation‐induced emission (AIE) probe initially designed for detecting amyloid fibers. This probe easily penetrates the membranes of the widely‐used prokaryotic model organism Escherichia coli, enabling the visualization of both amorphous aggregates and amyloid fibers through near‐infrared fluorescence. Notably, the probe exhibits sensitivity in distinguishing the varying aggregation propensities of proteins, regardless of whether they form amorphous aggregates or amyloid fibers in vivo. These properties contribute to the successful application of the QM‐FN‐SO3 probe in the subsequent investigation of the antiaggregation activities of two outer membrane protein (OMP) chaperones, both in vitro and in their physiological environment. Overall, our work introduces a near‐infrared fluorescent chemical probe that can quantitatively detect amyloid fibers and amorphous aggregates with high sensitivity in vitro and in vivo. Furthermore, it demonstrates the applicability of the probe in chaperone biology and its potential as a high‐throughput screening tool for protein aggregation inhibitors and folding factors. [ABSTRACT FROM AUTHOR]

Unpredictable in vivo therapeutic feedback of reactive oxygen species (ROS) efficiency is the major bottleneck of photodynamic therapy (PDT). Herein, novel PDT‐based nanotheranostics Pa–Mn&CH‐A@P are elaborately constructed for in vivo tracking biodistribution and in situ self‐reporting PDT, which innovatively unites magnetic resonance imaging (MRI) and chemiluminescence (CL) signals. Taking advantages of the versatility of lanthanide coordination chemistry and flash nanoprecipitation (FNP) technology, photosensitizers, MRI, and CL agents are unprecedently integrated within a stable and uniform nanotheranostic. Specifically, MRI signal offers detailed dose distribution of nanotheranostics with high‐spatial resolution, and CL signal timely performs in situ evaluation of ROS generation with high sensitivity. This dual‐modal MRI/CL nanotheranostic makes a breakthrough in high fidelity feedback for oral tumor, conquering the inherent unpredictable obstacles on spatially and sensitively reporting PDT. [ABSTRACT FROM AUTHOR]

Fluorescent compounds with aggregation-induced emission (AIE) characteristics (or AIEgens) have garnered significant research interest for various applications. The establishment of new AIE mechanisms coupled with quantitative prediction power is crucial to accelerate the development of novel AIE materials. Herein, we report the discovery of a new AIE mechanism, known as restriction of intramolecular bending (RIB), using computational chemistry and experimental validation. In RIB, the structural bending of the fluorophore scaffold caused by steric effects leads to fluorescence quenching in a dilute solution; fluorescence is only recovered in the aggregate state when the bending is inhibited. This RIB mechanism affords a practical guide for the quantitative molecular design of AIEgens, i.e., by converting traditional aggregation-caused quenching (ACQ) fluorophores to AIEgens through simple structural modifications. We believe that the introduction of the RIB mechanism paves a new avenue for the rational development of functional AIEgens. [ABSTRACT FROM AUTHOR]