Photosensitive AIEgens sensitize bacteria to oxidative damage and modulate the inflammatory responses of macrophages to salvage the photodynamic therapy against MRSA.

The urgent need for antimicrobial agents to combat infections caused by multidrug-resistant bacteria facilitates the exploration of alternative strategies such as photosensitizer (PS)-mediated photoinactivation. However, increasing studies have discovered uncorrelated bactericidal activities among PSs possessing similar photodynamic and pathogen-targeted properties. To optimize the photodynamic therapy (PDT) against infections, we investigated three type-I PSs of D-π-A AIEgens TI, TBI, and TTI. The capacities of reactive oxygen species (ROS) generation of TI, TBI, and TTI did not align with their bactericidal activities. Despite exhibiting the lowest photodynamic efficiency, TI exhibited the highest activities against methicillin-resistant Staphylococcus aureus (MRSA) by impairing the anti-oxidative responses of bacteria. By comparison, TTI, characterized by the strongest ROS production, inactivated intracellular MRSA by potentiating the inflammatory response of macrophages. Unlike TI and TTI, TBI, despite possessing moderate photodynamic activities and inducing ROS accumulation in both MRSA and macrophages, did not exhibit any antibacterial activity. Therefore, relying on the disturbed anti-oxidative metabolism of pathogens or potentiated host immune responses, transient ROS bursts can effectively control bacterial infections. Our study reevaluates the contribution of photodynamic activities of PSs to bacterial elimination and provides new insights into discovering novel antibacterial targets and agents.

Giant Flexoelectricity in Bent Semiconductor Thinfilm.

We elucidate the flexoelectricity of semiconductors in the high strain gradient regime, the underlying mechanism of which is less understood. By using the generalized Bloch theorem, we uncover a strong flexoelectric-like effect in bent thinfilms of Si and Ge due to a high-strain-gradient-induced band gap closure. We show that an unusual type-II band alignment is formed between the compressed and elongated sides of the bent film. Therefore, upon the band gap closure, electrons transfer from the compressed side to the elongated side to reach the thermodynamic equilibrium, leading to a pronounced change of polarization along the film thickness dimension. The obtained transverse flexoelectric coefficients are unexpectedly high with a quadratic dependence on the film thickness. This new mechanism is extendable to other semiconductor materials with moderate energy gaps. Our findings have important implications for the future applications of flexoelectricity in semiconductor materials.

Visualization of photothermal therapy by semiconducting polymer dots mediated photoacoustic detection in NIR II.

Visualization of photothermal therapy mediated by photothermal transduction agents (PTAs) is important to promote individual treatment of patients with low side effects. Photoacoustic detection has emerged as a promising noninvasive method for the visualization of PTAs distribution but still has limitations in temperature measurement, including poor measurement accuracy and low tissue penetration depth. In this study, we developed biocompatible semiconducting polymer dots (SPD) for in situ coupling of photothermal and photoacoustic detection in the near-infrared II window. SPD has dual photostability under pulsed laser and continuous-wave laser irradiation with a photothermal conversion efficiency of 42.77%. Meanwhile, a strong correlation between the photoacoustic signal and the actual temperature of SPD can be observed. The standard deviation of SPD-mediated photoacoustic thermometry can reach 0.13 °C when the penetration depth of gelatin phantom is 9.49 mm. Preliminary experimental results in vivo show that SPD-mediated photoacoustic signal has a high signal-to-noise ratio, as well as good performance in temperature response and tumor enrichment. Such a study not only offers a new nanomaterial for the visualization of photothermal therapy but will also promote the theranostic platform for clinical applications.

Synchronously Manipulating Absorption and Extinction Coefficient of Semiconducting Polymers via Precise Dual-Acceptor Engineering for NIR-II Excited Photothermal Theranostics.

Integrating the ultralong excitation wavelength, high extinction coefficient, and prominent photothermal conversion ability into a single photothermal agent is an appealing yet significantly challenging task. Herein, a precise dual-acceptor engineering strategy is exploited for this attempt based on donor-acceptor (D-A) type semiconductor polymers by subtly regulating the molar proportions of the two employed electron acceptor moieties featuring different electronic affinity and π-conjugation degrees, and making full use of the active intramolecular motion-induced photothermal effect. The optimal polymer SP4 synchronously shows desirable second near-infrared (NIR-II) absorption, an extremely high extinction coefficient, and satisfactory photothermal conversion behavior. Consequently, the unprecedented performance of SP4 NPs on 1064 nm laser-excited photoacoustic imaging (PAI)-guided photothermal therapy (PTT) is demonstrated by the precise tumor diagnosis and complete tumor elimination.

Double-pronged Antimicrobial Agents based on a Donor-π-Acceptor Type Aggregation-Induced Emission Luminogen.

Novel antibacterial agents are urgently needed to control the infections induced by multidrug-resistant (MDR) bacteria. Herein, we rationally designed and facilely synthesized a new D-π-A type luminogen with strong red/near-infrared fluorescence emission, great aggregation-induced emission (AIE) features, and excellent reactive oxygen species (ROS) production. The newly developed molecule TTTh killed the methicillin-resistant Staphylococcus aureus (MRSA) by triggering the ROS accumulation in bacteria and interrupting the membrane integrity. Moreover, TTTh specifically targeted the lysosomes and potentiated their maturation to accelerate the clearance of intracellular bacteria. Additionally, reduced bacterial burden and improved healing were observed in TTTh-treated wounds with negligible side effects. Our study expands the biological design and application of AIE luminogens (AIEgens), and provides new insights into discovering novel antibacterial targets and agents.

Bioinspired Supramolecular Nanotoroids with Aggregation-Induced Emission Characteristics.

Supramolecular toroids have attracted continuous attention because of their fascinating topological structure and important role in biological systems. However, it still remains a great challenge to construct supramolecular functional toroids and clarify the formation mechanism. Herein, we develop a strategy to prepare supramolecular helical fluorescent nanotoroids by cooperative self-assembly of an amino acid and a dendritic amphiphile (AIE-den-1) with aggregation-induced emission characteristics. Mechanistic investigation on the basis of fluorescence and circular dichroism analyses suggests that the toroid formation can be driven by the interactions of AIE-den-1 with amino acid and goes through a topological morphology transformation from nanofibers to left-handed nanotoroids by means of a twist-fused-loop process.

A potent luminogen with NIR-IIb excitable AIE features for ultradeep brain vascular and hemodynamic three-photon imaging.

Three-photon excited fluorescence microscopy (3PEFM) has emerged as a promising protocol for visualizing deep-brain vasculature and hemodynamics. However, the current situation is still far from satisfactory, due to small excitation action cross-section and short excitation wavelength of those previously reported 3PEFM luminogens. Herein, we manipulated molecular engineering by subtly regulating structural planarization/twisting to achieve ingenious integration of large three-photon absorption cross-section, high fluorescence quantum yield, ultralong near-infrared IIb excitation, and aggregation-induced emission features. The resulting molecule, namely DPCZ-BT, exhibited as high as 50.6% of fluorescence quantum yield and as large as 2.0 × 10-81 cm6s2/photon2 of three-photon absorption cross-section, which can be excited by 1665 nm fs laser and presents a recorded penetration depth of 1860 µm for deep-brain vascular structural imaging with high spatiotemporal resolution and signal-to-background ratio. Moreover, DPCZ-BT having good photostability and excellent biocompatibility is capable of impressively approaching 1600 µm depth in monitoring red blood cells flow velocity with extraordinary clarity for hemodynamics.

Deep-Brain Three-Photon Imaging Enabled by Aggregation-Induced Emission Luminogens with Near-Infrared-III Excitation.

Understanding the morphology and hemodynamics of cerebral vasculature at large penetration depths and microscale resolution is fundamentally important to decipher brain diseases. Among the various imaging technologies, three-photon (3P) microscopy is of significance by virtue of its deep-penetrating capability and submicron resolution, which especially benefits in vivo vascular imaging. Aggregation-induced emission luminogens (AIEgens) have been recognized to be extraordinarily powerful as 3P probes. However, systematic studies on the structure-performance relationship of 3P AIEgens have been seldom reported. Herein, a series of AIEgens has been designed and synthesized. By intentionally introducing benzene rings onto electron donors (D) and acceptors (A), the molecular distortion, conjugation strength, and the D-A relationship can be facilely manipulated. Upon encapsulation with DSPE-PEG2000, the optimized AIEgens are successfully applied for 3P microscopy with emission in the far-red/near-infrared-I (NIR-I, 700-950 nm) region under the near-infrared-III (NIR-III, 1600-1870 nm) excitation. Impressively, using mice with an opened skull, vasculature within 1700 µm and a microvessel with a diameter of 2.2 µm in deep mouse brain were clearly visualized. In addition, the hemodynamics of blood vessels were well-characterized. Thus, this work not only proposes a molecular design strategy of 3P AIEgens but also promotes the performance of 3P imaging in cerebral vasculature.

Mixed-Valence CsCu4Se3: Large Phonon Anharmonicity Driven by the Hierarchy of the Rigid [(Cu+)4(Se2-)2](Se-) Double Anti-CaF2 Layer and the Soft Cs+ Sublattice.

Crystalline solids that exhibit inherently low lattice thermal conductivity (κlat) have attracted a great deal of attention because they offer the only independent control for pursuing a high thermoelectric figure of merit (ZT). Herein, we report the successful preparation of CsCu4Q3 (Q = S (compound 1), Se (compound 2)) with the aid of a safe and facile boron-chalcogen method. The single-crystal diffraction data confirm the P4/mmm hierarchical structures built up by the mixed-valence [(Cu+)4(Q2-)2](Q-) double anti-CaF2 layer and the NaCl-type Cs+ sublattice involving multiple bonding interactions. The electron-poor compound CsCu4Q3 features Cu-Q antibonding states around EF that facilitates a high σ value of 3100 S/cm in 2 at 323 K. Significantly, the ultralow κlat value of 2, 0.20 W/m/K at 650 K (70% lower than that of Cu2Se), is mainly driven by the vibrational coupling of the rigid double anti-CaF2 layer and the soft NaCl-type sublattice. The hierarchical structure increases the bond multiplicity, which eventually leads to a large phonon anharmonicity, as evidenced by the effective scattering of the low-lying optical phonons to the heat-carrying acoustic phonons. Consequently, the acoustic phonon frequency in 2 drops sharply from 118 cm-1 (of Cu2Se) to 48 cm-1. In addition, the elastic properties indicate that the hierarchical structure largely inhibits the transverse phonon modes, leading to a sound velocity (1571 m/s) and a Debye temperature (189 K) lower than those of Cu2Se (2320 m/s; 292 K).