Sequence-Responsive Multifunctional Supramolecular Nanomicelles Act on the Regression of TNBC and Its Lung Metastasis via Synergic Pyroptosis-Mediated Immune Activation.

Design of effective nanodrugs to modulate the immunosuppression of tumor microenvironment is a desirable approach to boost the clinical tumor-therapeutic effect. Supramolecular nanomicelles PolyMN-TO-8, which are constructed by self-assembling supramolecular host MTX-MPEG2000, guest NPX-2S, and TO-8 through hydrophobic forces, have excellent stability and responsiveness to carboxylesterase and glutathione in turn. In vivo studies validate that PolyMN-TO-8 enable to trigger pyroptosis-mediated immunogenic cell death under laser, avoiding the occurrence of immune dysregulation simultaneously. This therapeutic mode strengthens dendritic cells' maturation and accelerates the infiltration of CD8+ T cells into tumors through moderate activation of pro-inflammatory factors with elimination of immune-escape, ultimately making the tumor inhibition rate as high as 87.44% via synergistic functions of photodynamic therapy, photothermal therapy, chemotherapy, etc. The loss of immune-escape quickens the infiltration of CD8+ T cells into lungs, and further eschews the generation of tumor nodules in it. Chemotherapy, the release of interferon-γ, and immune memory effect also strengthen the defense against metastasis. The generation of O2 catalyzed by PolyMN-TO-8 under laser is indispensable for tumor metastasis inhibition undoubtedly.

A mitochondria-targeted single fluorescence probe for separately and continuously visualizing H2S and Cys with multi-response signals.

Hydrogen sulfide and cysteine are momentous endogenous regulators of many physiological processes and maintain a dynamic balance of redox in living organisms. To investigate the inter-relationship of them in vivo, there is a pressing need to develop analytical molecular tools to identify related biomolecules. We construct a mitochondria-targeted single fluorescence probe (Mit-CM) for separately and continuously visualizing H2S, Cys and H2S/Cys with multi-response fluorescence signals. Mit-CM has the following advantages: (Ⅰ) colorimetric and ratiometric: two well-separated emission bands can ensure accurate detection of the analyte and significant color changes contribute to rapid identification of the analyte by the naked eye; (Ⅱ) mitochondrial localization: study the physiological functions of H2S and Cys in mitochondria; (Ⅲ) separate and continuous detection of H2S and Cys: reveal the inter-relationship and interconversion of them in biological system. Moreover, the desirable attributes of low cytotoxicity, better biocompatibility and excellent mitochondria enrichment ability indicate that Mit-CM can be employed to achieve detection and observe distribution of H2S, Cys and H2S/Cys in living organism.

Molecular Engineering of Thermally Activated Delayed Fluorescence Emitters with Aggregation-Induced Emission via Introducing Intramolecular Hydrogen-Bonding Interactions for Efficient Solution-Processed Nondoped OLEDs.

Purely organic luminescent materials concurrently exhibiting thermally activated delayed fluorescence (TADF) and aggregation-induced emission (AIE) features are in great demand due to their high efficiency in aggregation-state toward efficient nondoped OLEDs. Herein, a class of TADF emitters adopting phenyl(pyridyl)methanone as electron-accepting segments and di(tert-butyl)carbazole and 9,9-dimethyl-9,10-dihydroacridine (or phenoxazine) as electron-donating groups are designed and synthesized. The existence of intramolecular hydrogen bonding is conducive to minish the energy difference between a singlet and a triplet (ΔEst), suppress nonradiative decay, and increase the luminescence efficiency. By using 3CPyM-DMAC as the emitter, the nondoped device via a solution process realize a high current efficiency (CE) and external quantum efficiency (EQE) of 35.4 cd A-1 and 11.4%, respectively, which is superior to that of CBM-DMAC with a CE and EQE of 14.3 cd A-1 and 6.7%. This work demonstrates a promising tactic to the establishment of TADF emitters with AIE features via introducing intramolecular hydrogen bonding.