Spatiotemporally Controllable Peptide‐Based Nanoassembly in Single Living Cells for a Biological Self‐Portrait

Abstract

Simultaneous precise localization and activity evaluation of a biomolecule in a single living cell is through an enzyme-specific signal-amplification process, which involves the localized, site-specific self-assembly, and activation of a presignaling molecule. The inactive presignaling tetraphenylethylene (TPE)-peptide derivative, TPE-YpYY, is nondetectable and highly biocompatible and these small molecules rapidly diffuse into living cells. Upon safely arriving at an active site, and accessing the catalytic pocket of an enzyme, TPE-YpYY immediately and quantitatively accumulates in situ in response to enzymatic activity, forms an enzyme anchor TPE-YYY nanoassembly, displays aggregation-induced emission behavior, and finally lights up the active enzyme, indicating its activity, and allowing its status in living cells to be tracked. This simple and direct self-portrait method can be used to monitor dynamic self-assembly processes in individual living cells and may provide new insights that reveal undiscovered biological processes and that aid in developing biomedical hybrid devices. In the future, this strategy of molecular design can be further expanded to the noninvasive investigation of other bioactive molecules, thus facilitating quantitative imaging.

Tandem Molecular Self‐Assembly in Liver Cancer Cells

“…These observations suggested that the tandem self‐assembly of 1 in the extra‐ and intracellular environments of liver cancer cells was due to the high concentrations of both ALP and GSH in liver cancer cells. Although intracellular self‐assembly has recently been demonstrated to be a powerful strategy for the spatiotemporal profiling of enzyme activity, those self‐assembled fluorescent probes did not show obvious fiber structures within the cells, while our results directly and clearly show the formation of intracellular fibers in liver cancer cells. It is important to note that the distribution of nanofibers was different between the QGY7703 and HepG2 cells.…”

AIE Stereoisomers with Huge Differences in Luminescence Behavior and Biomedical Activity

“…As the cellular uptake of E/Z-TPAN-OM and E/Z-TPAN-OH was limited, E/Z-TPAN-POH modified with phosphate group were further designed to improve their water solubilities and endow them with enzymatic responsiveness, as the phosphate group is the substrate of alkaline phosphatase (ALP) that plays a significant role in cell signaling pathway and has become an important biomarker in cancer diagnosis. [50][51][52][53] The obtained E/Z-TPAN-OM isomers retained the same stereo-structure as their individual precursor and displayed different fluorescence quantum yields. As the E/Z-TPAN-POH and their hydrolysis product, E/Z-TPAN-OH (Figure 7a), eluted out with different time scales, the ALP-catalyzed hydrolysis of E/Z-TPAN-POH could therefore be quantitatively monitored by HPLC.…”

AIE Stereoisomers with Huge Differences in Luminescence Behavior and Biomedical Activity

“…modified with phosphate group were further designed to improve their water solubilities and endow them with enzymatic responsiveness, as the phosphate group is the substrate of alkaline phosphatase (ALP) that plays a significant role in cell signaling pathway and has become an important biomarker in cancer diagnosis. [50][51][52][53] The obtained E/Z-TPAN-OM isomers retained the same stereo-structure as their individual precursor and displayed different fluorescence quantum yields. As the E/Z-TPAN-POH and their hydrolysis product, E/Z-TPAN-OH (Figure 7a), eluted out with different time scales, the ALP-catalyzed hydrolysis of E/Z-TPAN-POH could therefore be quantitatively monitored by HPLC.…”