Dual-modal imaging-guided agent based on NIR-II aggregation-induced emission luminogens with balanced phototheranostic performance.

Phototherapy has garnered considerable interest for its potential to revolutionize conventional cancer treatment. Organic materials with near-infrared II (NIR-II, 1000-1700 nm) fluorescence and photothermal effects are key for precise tumor diagnosis and treatment, yet optimizing their output for higher resolution and reduced photodamage remains a challenge. Herein, a multifunctional NIR-II photosensitizer (LSC) has been developed using the aggregation-induced emission (AIE) technology. The utilization of thieno[3,2-b]thiophene as an electron-rich and bulky donor/acceptor bridge has allowed for the elongation of conjugation length and distortion of the AIE main chain. This strategic modification effectively enhances the electron push-pull effect, endowing the LSC with a Stokes shift of over 400 nm and AIE characteristics. We have successfully built-up stable nanoparticles called FA-LSC NPs using a nano-precipitation method. These nanoparticles exhibit high NIR-II fluorescent brightness (ε × QY = 1064 M-1 cm-1) and photothermal conversion efficiency (41%). Furthermore, the biocompatible FA-LSC NPs demonstrate effective tumor accumulation and exceptional photothermal therapeutic efficacy both in vitro and in vivo. These nanoparticles were applied to fluorescence-photothermal dual-mode imaging-guided photothermal ablation in a HeLa tumor xenograft mouse model, resulting in favorable photothermal clearance outcomes.

Folding and Unfolding of a Fully Synthetic Transmembrane Receptor for ON/OFF Signal Transduction.

Signal transduction processes in living organisms are mainly transmitted through conformational changes in transmembrane protein receptors. So far, the development of signal transduction models induced by artificial simulation of conformational changes remains limited. We herein report a new artificial receptor that achieves controllable "ON/OFF" signal transduction through conformational changes between the folding and unfolding of a transmembrane foldamer moiety. The receptor contains three functional modules: a lipid-anchored cholic acid headgroup, a foldamer transmembrane moiety, and a precatalyst tailgroup. After inserting in the lipid membrane, the addition of Zn2+ induces unfolding of the foldamer, which changes the molecular conformation and activates the tailgroup to enter the cavity to perform its catalytic task, resulting in signal transduction in an "ON" state. By further adding a competitive ligand to bind Zn2+, the transduction can be turned "OFF". External signals can be used to reversibly switch intravesicular catalysis on and off, which provides a new model for constructing artificial signal transduction systems.

A rigid-axle-based molecular rotaxane channel facilitates K+/Cl- co-transport across a lipid membrane.

Inspired by the design criteria of heteroditopic receptors for ion-pair binding, we herein describe a new strategy to construct a rotaxane transporter (RR[2]) for K+/Cl- co-transport. The use of a rigid axle improves the transport activity with an EC50 value of 0.58 µM, presenting a significant step toward developing rotaxane artificial channels.

A Light-Driven Molecular Machine Controls K+ Channel Transport and Induces Cancer Cell Apoptosis.

The design of artificial ion channels with high activity, selectivity and gating function is challenging. Herein, we designed the light-driven motor molecule MC2, which provides new design criteria to overcome these challenges. MC2 forms a selective K+ channel through a single molecular transmembrane mechanism, and the light-driven rotary motion significantly accelerates ion transport, which endows the irradiated motor molecule with excellent cytotoxicity and cancer cell selectivity. Mechanistic studies reveal that the rotary motion of MC2 promotes K+ efflux, generates reactive oxygen species and eventually activates caspase-3-dependent apoptosis in cancer cells. Combined with the spatiotemporally controllable advantages of light, we believe this strategy can be exploited in the structural design and application of next-generation synthetic cation transporters for the treatment of cancer and other diseases.

Precise macroscopic supramolecular assembly of photopatterned hydrogels.

Here we demonstrate that a precise macroscopic supramolecular assembly (MSA) can be achieved using a surface photopatterning strategy. The electrostatic interaction of the photopatterned polyelectrolytes drives hydrogel cuboids to form a stable MSA on a millimeter scale and the spatial controllability of light enables the hydrogels to be assembled into complex supramolecular architectures.

A Synthetic Phospholipid Derivative Mediates Ion Transport Across Lipid Bilayers.

Inspired by the natural phospholipid structures for cell membrane, a synthetic phospholipid LC with an ion recognition group benzo-18-crown-6 (B18C6) moiety was prepared which has been demonstrated to be able to transport ions across the lipid bilayers. Fluorescent vesicle assay shows that LC has an excellent transport activity, and the EC50 value for K+ is 11.2 µM. The voltage clamp measurement exhibits regular square-like current signals with considerably long opening times, which indicates that LC achieves efficient ion transport through a channel mechanism and its single channel conductivity is 17 pS. Both of the vesicle assay and patch clamp tests indicate that LC has selectivity for Rb+, whose ionic radius is larger than the cavity of crown ether. It suggests that the sandwich interaction may play a key role in the ion transport across lipid bilayers. All these results help us to speculate that LC transports ions via a channel mechanism with a tetrameric aggregate as the active structure. In addition, LC had obvious toxicity to HeLa cells, and the IC50 was 100.0 µM after coculture for 36 h. We hope that this simple synthetic phospholipid will offer novel perspectives in the development of more efficient and selective ion transporters.