Tumortherapeutika Pyridiniumsubstituierte Tetraphenylethylen‐Salze können Autophagie induzieren und gleichzeitig den Autophagieflux hemmen. R. Zhao, D. Zhang et al. berichten in ihrem Forschungsartikel auf S. 10128, wie diese Ergebnisse neue Funktionalitäten für AIEgene aufzeigen.

Herein, a new fluorescence turn-on chemosensor 2-(4-(1,2,2-triphenylvinyl)phenoxy)acetic acid (TPE-COOH) specific for Al(3+) was presented by combining the aggregation-induced-emission (AIE) effect of tertaphenylethylene and the complexation capability of carboxyl. The introduction of carboxylic group provides the probe with good water-solubility which is important for analyzing biological samples. The recognition toward Al(3+) induced the molecular aggregation and activated the blue fluorescence of the TPE core. The high selectivity of the probe was demonstrated by discriminating Al(3+) over a variety of metal ions in a complex mixture. A detection limit down to 21.6 nM was determined for Al(3+) quantitation. Furthermore, benefiting from its good water solubility and biocompatibility, imaging detection and real-time monitoring of Al(3+) in living HeLa cells were successfully achieved. The AIE effect of the probe enables high signal-to-noise ratio for bioimaging even without multiple washing steps. These superiorities make this probe a great potential for the functional study and analysis of Al(3+) in complex biosystems.

Metal–peptide interactions provide plentiful resource and design principles for developing functional biomaterials and smart sensors. Pb2+, as a borderline metal ion, has versatile coordination modes. The interference from competing metal ions and endogenous chelating species greatly challenges Pb2+ analysis, especially in complicated living biosystems. Herein, a biomimetic peptide-based fluorescent sensor GSSH-2TPE was developed, starting from the structure of a naturally occurring peptide glutathione. Lewis acid–base theory was employed to guide the molecular design and tune the affinity and selectivity of the targeting performance. The integration of peptide recognition and aggregation-induced emission effect provides desirable sensing features, including specific turn-on response to Pb2+ over 18 different metal ions, rapid binding, and signal output, as well as high sensitivity with a detection limit of 1.5 nM. Mechanism investigation demonstrated the balance between the chelating groups, and the molecular configuration of the sensor contributes to the high selectivity toward Pb2+ complexation. The ion-induced supramolecular assembly lights up the bright fluorescence. The ability to image Pb2+ in living cells was exhibited with minimal interference from endogenous biothiols, no background fluorescence, and good biocompatibility. With good cell permeability, GSSH-2TPE can monitor changes in Pb2+ levels and biodistribution and thus predict possible damage pathways. Such metal–peptide interaction-based sensing systems offer tailorable platforms for designing bioanalytical tools and show great potential for studying the cell biology of metal ions in living biosystems.

Peptides with modular structure provide a tailorable platform for constructing responsive supramolecular assemblies, which are attractive as functional biomaterials and smart sensors. In this work, the feasibility of regulating small peptides assembly with molecular design and metal ion recognition was demonstrated. Tripeptides were designed and found to have diverse response and self-assembly behavior to Hg. The incorporation of an aggregation-induced emission fluorophore TPE enabled the visualization of Hg recognition and the assembly phenomenon. A structural analogue (Pep2) to γ-glutathione was identified with high specificity and nanomolar response to Hg both in buffer solution and living cells. Driven by the coordination force and noncovalent intramolecular stacking, assembling of twisted nanofibers from Pep2-TPE and Hg were observed. Benefiting from its biocompatibility, fast and switchable fluorescence response, Pep2-TPE was applied for imaging and monitoring Hg distribution in living cells and zebrafish. With good permeability to plasma membrane and tissues, Pep2-TPE indicated the preferential distribution of Hg in cell nucleoli and brain of zebrafish, which is related with the deleterious effect of inorganic mercury in living biosystems.

A fast and sensitive method was established for an in-solution selection of cancer cell-targeting peptides at "single-residue resolution" by using the switchable fluorescence of tetraphenylethylene. The selected peptides have potential for biomarker tracing and can be used for targeted delivery of different cargos into living cancer cells.

Nonselectivity and drug resistance are two major obstacles for cancer treatment. Although great advances have been made toward cell targeting or discovering novel delivery pathways, it is still desirable to simultaneously overcome the two hurdles for successful cancer theranostics. Herein, a peptide-guided system was tailored by modular integration of a cancer biomarker-specific peptide, a mitochondria-targeting motif and a cell toxin. Cell imaging analysis revealed that the dual-targeting peptide-drug conjugate (PDC) features in cancer cell-specific uptake, strong drug retention, and programmable intracellular translocation. Facilitated by in situ bond cleavage, PDC successfully diverted the toxic effect of nucleus-localized drug to mitochondria. Mechanism investigation demonstrated that the cell damage pathway of the drug was also transformed, which is beneficial to reverse drug resistance in cancer cells. The effectiveness of PDC for cancer therapy was further demonstrated by in vivo imaging and tumor inhibition assay. With intravenous injection, targeted accumulation in the tumor site, and tumor suppressing efficacy without side effects exhibit its perspective for cancer treatment. The dual-targeting peptidedrug conjugate featuring tailored transportation route highlights a promising and generally applicable way to enhance the overall therapeutic index of conventional anticancer drugs.

Significant efforts have been devoted to developing trace-level quantification of Hg2+.

Tuning autophagy in a controlled manner could facilitate cancer therapy but it remains challenging. Pyridinium‐substituted tetraphenylethylene salts (PTPE 1—3), able to target mitochondria and disrupt autophagy after forming complexes with albumin, are reported. Mitochondrion affinity and autophagy‐inducing activity are improved by prolonging the length of alkyl chains in PTPE 1–3. PTPE 1–3 demonstrate proautophagic activity and a mitophagy blockage effect. Failure of autophagosome–lysosome fusion in downstream autophagy flux results in cancer cell death. Moreover, fast formation of complexes of PTPE 1–3 with albumin in blood can facilitate biomimetic delivery and deep tumor penetration. Efficient tumor accumulation and effective tumor suppression are successfully demonstrated with in vitro and in vivo studies. PTPE 1–3 salts exhibit dual functionality: they target and image mitochondria because of aggregation‐induced emission effects and they are promising for cancer therapy.