Article-Journal

Photodynamic therapy (PDT) is a minimally invasive therapeutic modality. However, the residual photosensitizers (PSs) after PDT can still produce toxic singlet oxygen (1O2) under sunlight to damage normal tissues. The PS that can be switched off after PDT is desirable but rare. Herein, we propose a general strategy to design effective and self-degradable PSs by embedding an anthracene bridge into donor–acceptor (D–A) structures. First, the steric anthracene can regulate the orbital distribution for enhancing the 1O2 production capacity. More importantly, the anthracene is responsive to the self-produced 1O2 for self-degradation. Besides, the degradation rate can be fine-tuned by the hydrophilicity of PSs. In this way, the PSs can realize a balance between treatment and suicide to ensure PDT and post-treatment safety. This work provides new insights into the design of degradable PSs with a clear mechanism, aiming to improve the post-safety of PDT.

Developing a ferroelectric tunnel junction with a robust polarization reversal is essential for errorless data storage, but it remains challenging since the second-order phase transition dominates the reversal and introduces intermediate states. This investigation has proposed a charge-gradient-induced ferroelectricity, which is featured with the first-order phase transition. As an order parameter, a charge-gradient-induced polarization is achieved by modulation of stoichiometric oxygen along the Bi2O2Se/Bi2Se3O9 bilayer during pulsed laser deposition. At room temperature, this polarity points out-of-plane and shows an abrupt reversal in the ferroelectric hysteresis loop. The coercive field only increases by 0.04 V/nm after 300 reversals. Fabricated into the ferroelectric tunnel junction, the bilayer ferroelectric exhibits a comparable electroresistance of 100. The ON/OFF state can be switched repeatedly or after a 360 s retention. Characterizations of scanning capacitance microscopy and the current–voltage relation demonstrate that the ON/OFF switching is based on an injection exchange between the tunnelling and the thermionic emission.

π-Molecules play important roles in many applications such as organic light-emitting devices, photocatalysis, photovoltaics, biosensors, and medicine. Very often, π-conjugated molecules with high utilization of excited states in the solid state are of great research interest. However, owing to the gap between molecular structure and effective molecular packing, there are very few designs toward π molecules with very high exciton utilization in the solid state. Herein, we report a new π skeleton, folded π, to achieve high exciton utilization in the solid state. Based on a “folded π” formula, 12 compounds with two or three folding π planes were designed and synthesized. We found that folded π molecules tend to form well-aligned 1D molecular columns of patterns (“box”, “braid”, or “stair”) with high packing energy, which is mainly contributed by numerous weak π interactions. As a result of effective suppression of molecular motion, all the compounds show very high exciton utilization in solids.

Three conjugated polymers that have the same donor–acceptor structure but totally different architectures are designed to show both Type-I and Type-II photosensitization abilities simultaneously, among which the hyperbranched polymer shows the best performance in both in vitro and in vivo experiments, superior to even the commonly used clinical photosensitizer of hemoporfin.

The pursuing of photosensitizers (PSs) with efficient reactive oxygen species (ROS) especially type I ROS generation in aggregate is always in high demand for photodynamic therapy (PDT) and photoimmunotherapy but remains to be a big challenge. Herein, we report a cationization molecular engineering strategy to boost both singlet oxygen and radical generation for PDT. Cationization could convert the neutral donor-acceptor (D-A) typed molecules with the dicyanoisophorone-triphenylamine core (DTPAN, DTPAPy) to their A-D-A′ typed cationic counterparts (DTPANPF6 and DTPAPyPF6). Our experiment and simulation results reveal that such cationization could enhance the aggregation-induced emission (AIE) feature, promote the intersystem crossing (ISC) processes, and increase the charge transfer and separation ability, all of which work collaboratively to promote the efficient generation of ROS especially hydroxyl and superoxide radicals in aggregates. Moreover, these cationic AIE PSs also possess specific cancer cell mitochondrial targeting capability, which could further promote the PDT efficacy both in vitro and in vivo. Therefore, we expect this delicate molecular design represents an attractive paradigm to guide the design of type I AIE PSs for the further development of PDT.

Porous organic cages (POCs) have many advantages, including superior microenvironments, good monodispersity, and shape homogeneity, excellent molecular solubility, high chemical stability, and intriguing host-guest chemistry. These properties enable POCs to overcome the limitations of extended porous networks such as metal-organic frameworks (MOFs) and covalent organic frameworks (COFs). However, the applications of POCs in bioimaging remain limited due to the problems associated with their rigid and hydrophobic structures, thus leading to strong aggregation-caused quenching (ACQ) in aqueous biological media. To address this challenge, we report the preparation of aggregation-induced emission (AIE)-active POCs capable of stimuli responsiveness for enhanced bioimaging. We rationally design a hydrophilic, structurally flexible tetraphenylethylene (TPE)-based POC that is almost entirely soluble in aqueous solutions. This POC’s conformationally flexible superstructure allows the dynamic rotation of the TPE-based phenyl rings, thus endowing impressive AIE characteristics for responses to environmental changes such as temperature and viscosity. We employ these notable features in the bioimaging of living cells and obtain good performance, demonstrating that the present AIE-active POCs are suitable candidates for further biological applications.

Ischemic stroke is a highly prevalent cause of mortality and morbidity. The only FDA-approved treatment is thrombolysis using tissue plasminogen activator (tPA), which possesses a short effective time window. Real-time recanalization monitoring is crucial to establish successful reperfusion and serves as a strong predictor of clinical outcomes. First-line clinical imaging techniques, such as computed tomography and magnetic resonance imaging, are limited in their soft-tissue resolution, scanning speed, and accessibility. Transcranial doppler ultrasound, the current gold standard for recanalization monitoring, is a blind technique and highly operator dependent. Herein, a photothermal-activatable liposome carrying tPA for photoacoustic (PA) image-guided therapy for real-time and precise recanalization monitoring of ischemic stroke is designed. The liposome containing an organic molecule with propeller structures exhibits excellent photothermal properties and significantly amplified PA signals as compared with the widely used polymer nanoparticles. Near-infrared (NIR) laser triggers rapid release of tPA for quick blood clot lysis in vitro. Administration of the liposome in a rat photothrombotic ischemia model facilitates high-resolution PA imaging for precise real-time recanalization assessment. Precisely controlled tPA release at the ischemic region is achieved by PA image-guided NIR laser irradiation, which successfully dissolves the blood clot and restores perfusion, making this design promising for translational applications.

Artificial intelligence (AI) based self-learning or self-improving material discovery system will enable next-generation material discovery. Herein, we demonstrate how to combine accurate prediction of material performance via first-principle calculations and Bayesian optimization-based active learning to realize a self-improving discovery system for high-performance photosensitizers (PSs). Through self-improving cycles, such a system can improve the model prediction accuracy (best mean absolute error of 0.090 eV for singlet–triplet spitting) and high-performance PS search ability, realizing efficient discovery of PSs. From a molecular space with more than 7 million molecules, 5357 potential high-performance PSs were discovered. Four PSs were further synthesized to show performance comparable with or superior to commercial ones. This work highlights the potential of active learning in first-principle-based materials design, and the discovered structures could boost the development of photosensitization related applications.

For practical applications, molecules often exist in an aggregate state. Therefore, it is of great value if one can predict the performance of molecules when forming aggregates, for example, aggregation-induced emission (AIE) or aggregation-caused quenching (ACQ). Herein, a database containing AIE/ACQ molecules reported in the literature is first established. Through training, these machine learning (ML) models can build up the structure-property relationship and thus implement fast prediction of AIE/ACQ properties. To this end, a multi-modal approach is proposed, multiple prediction methods are compared and designed, and thus an ensemble strategy is developed. First, multiple molecular descriptors are considered at the same time, major features are extracted by dimensionality reduction, and multi-modal features are synthesized. Then, several state-of-the-art methods are designed and compared to analyze the advantages of the different methods. Finally, the ensemble strategy combines the advantages of the multiple methods to obtain the final prediction result. The reliability of this approach in an unknown molecular space is further verified by three newly designed molecules. Reasonable consistency between model predictions and experimental outcomes is obtained. The result indicates that ML can be a powerful tool to predict molecular properties in the aggregated state, thus accelerating the development of solid-state optical materials.

The electrochemical oxidation of DNA mediated by [Ru(bpy)2tatp]2+ (bpy = 2,2′-bipyridine, tatp = 1,4,8,9-tetra-aza-triphenylene) upon incorporation of [Co(phen)3]3+ (phen = 1,10-phenanthroline) has been investigated. The results from emission spectra and fluorescence microscope images suggest the formation of an aggregate containing [Ru(bpy)2tatp]2+, DNA and [Co(phen)3]3+ based on the strong interactions. The evidences from repetitive differential pulse voltammograms and cyclic voltammogams reveal that the presence of [Co(phen)3]3+ can promote the oxidation of DNA mediated by [Ru(bpy)2tatp]2+ on an indium tin oxide (ITO) electrode. The oxidative response of DNA shows a cumulative enhancement with increasing the voltammetric sweeping number, and a stable linear response to DNA is found between 0.001 mM and 0.1 mM. Furthermore, the oxidative mechanism of DNA mediated by [Ru(bpy)2tatp]2+ upon incorporation of [Co(phen)3]3+ becomes evident, depending on the concentration of DNA and mediators, the structure of mediators and scan rate. The results from this study provide a significant basis for better understanding the oxidative damage of DNA mediated by DNA-binding agents.