Trapping endoplasmic reticulum with amphiphilic AIE-active sensor via specific interaction of ATP-sensitive potassium (KATP)

Abstract

The current aggregation-induced emission luminogens (AIEgens) sometimes suffer from poor targeting selectivity due to undesirable aggregation in hydrophilic biosystem with “always-on” fluorescence or unspecific aggregation in lipophilic organelle with premature activated fluorescence. Herein, we report an unprecedented “amphiphilic AIEgen” sensor QM-SO3-ER based on the AIE building block of quinoline-malononitrile (QM). The introduced hydrophilic sulfonate group can well control the specific solubility in hydrophilic system with desirable initial “fluorescence-off” state. Moreover, the incorporated p-toluenesulfonamide group plays two roles: enhancing the lipophilic dispersity, and behaving as binding receptor to the ATP-sensitive potassium (KATP) on endoplasmic reticulum (ER) membrane to generate the docking assay confinement effect with targetable AIE signal. The amphiphilic AIEgen has for the first time well settled down the predicament of unexpected “always-on” fluorescence in aqueous system and untargetable aggregation signal in lipophilic organelle before binding to ER, thus successfully overcoming the bottleneck of AIEgen targetability.

Spatiotemporal Visualization of Cell Membrane with Amphiphilic Aggregation-Induced Emission-Active Sensor

“…In order to avoid the premature activated fluorescence caused by unspecific aggregations in reported AIE sensors, 25,26 we rationally design and construct an amphiphilic AIE-active probe step by step. 27,28 In our strategy, firstly, the newly developed AIE building block, quinoline-malononitrile (QM), was employed as the core structure to overcome the ACQ effect of commercial probes (Figure S1) and the π-conjugated backbone dimethylamino benzene was utilized to extend the emission wavelength as QM-PN. [29][30][31][32][33] Then, the electronwithdrawing pyridine group was introduced to further extend emission wavelength, affording the intermediate Py-QM-PN.…”

“…The wavelength extension from QM to QMC12 was realized by enhancing the electronic donor-acceptor effect, in which the absorption successfully shifted from 414 nm of QM to 455 nm of QMC12, and the emission peak red shifted from 514 nm of QM to 628 nm of QMC12 (Figure S7). 28 According to Density functional theory (DFT) calculations the highest occupied molecular orbital (HOMO) electron density of QMC12 is mainly delocalized at the electron-rich unit N,N'-dimethylamino and phenyl group, and the lowest unoccupied molecular orbital (LUMO) is mainly delocalized at pyridinium salt group (Figure 2M and Figure S8). The smaller HOMO-LUMO energy gap of QMC12 further confirmed the stronger electronic donating-accepting interaction, which is the reason for the longer absorption wavelength.…”

AIE-active luminogens as highly efficient free-radical ROS photogenerator for image-guided photodynamic therapy

“…24 In addition, AIEgens with “off–on” fluorescence could realize higher-fidelity imaging compared to ACQ fluorophores, especially in terms of decreasing false fluorescence signals. 25–28…”

An aggregation-induced emission platform for efficient Golgi apparatus and endoplasmic reticulum specific imaging

“… 30 However, there are limited examples of AIE probes that are capable of staining the GA 31 and ER. 32 They were designed based on different AIE-active fluorophores with tedious synthesis and complicated purification. What's worse, the specificity of some probes is far from ideal with only a moderate Pearson's correlation coefficient.…”