Pyridinium-Yne Click Polymerization: A Facile Strategy toward Functional Poly(Vinylpyridinium Salt)s with Multidrug-Resistant Bacteria Killing Ability.

Polymeric materials with antibacterial properties hold great promise for combating multidrug-resistant bacteria, which pose a significant threat to public health. However, the synthesis of most antibacterial polymers typically involves complicated and time-consuming procedures. In this study, we demonstrate a simple and efficient strategy for synthesizing functional poly(vinylpyridinium salt)s via pyridinium-yne click polymerization. This click polymerization could proceed with high atom economy under mild conditions without any external catalyst, yielding soluble and thermally stable poly(vinylpyridinium salt)s with satisfactory molecular weights and well-defined structures in excellent yields. Additionally, the incorporation of luminescent units such as fluorene, tetraphenylethylene, and triphenylamine into the polymer backbone confers excellent aggregation-enhanced emission properties upon the resulting polymers, rendering them suitable for bacterial staining. Moreover, the existence of pyridinium salt imparts intrinsic antibacterial activity against multidrug-resistant bacteria to the polymers, enabling them to effectively inhibit wound bacterial infection and significantly expedite the healing process. This work not only provides an efficient method to prepare antibacterial polymers, but also opens up the possibility of various applications of polymers in healthcare and other antibacterial fields.

Cascade C-H-Activated Polyannulations toward Ring-Fused Heteroaromatic Polymers for Intracellular pH Mapping and Cancer Cell Killing.

The development of straightforward and efficient synthetic methods toward ring-fused heteroaromatic polymers with attractive functionalities has great significance in both chemistry and materials science. Herein, we develop a facile cascade C-H-activated polyannulation route that can in situ generate multiple ring-fused aza-heteroaromatic polymers from readily available monomers in an atom-economical manner. A series of complex polybenzimidazole derivatives with high absolute molecular weights of up to 24 000 are efficiently produced in high yields within 2 h. Benefiting from their unique imidazole-containing ring-fused structures with multiple aryl pendants, the obtained polymers show excellent thermal and morphological stability, good solution processability, high refractive index, small chromic dispersion, as well as remarkable acid-base-responsive fluorescence. Taking advantage of the ratiometric fluorescence response of the triphenylamine-substituted heteroaromatic polymer to pH variations, we successfully apply it as a sensitive fluorescence probe for the mapping and quantitative analysis of intracellular pH in live cells. Furthermore, through the simple N-methylation reaction of the ring-fused polybenzimidazoles, diverse azonia-containing polyelectrolytes are readily produced, which can efficiently kill cancer cells via the synergistic effects of dark toxicity and phototoxicity.

Lysosome-Targeting Red-Emitting Aggregation-Induced Emission Probe with Large Stokes Shift for Light-Up in Situ Visualization of ß-N-Acetylhexosaminidase.

Lysosomal ß-N-acetylhexosaminidase (Hex) has been reported to possess unique physiological performances. Detection and visualization of Hex in lysosome will be favorable to reveal the basis of its functions. However, Hex-specific fluorescent probes are rarely reported. In this study, we reported the first lysosome-targeting Hex-lighting-up aggregation-induced emission (AIE)-active fluorescent probe (GlcNAc-TPE) with remarkably large Stokes shift and high sensitivity and selectivity. GlcNAc-TPE can selectively locate in lysosome and visualize endogenous Hex in live HCT116 cells and in live mice with high stability and good biocompatibility, providing a useful AIE probe for real-time visualization of Hex in live samples.

The development and characterization of a stable Coxsackievirus A16 infectious clone with Nanoluc reporter gene.

Coxsackievirus A16 (CA16) belongs to the Human Enterovirus A species, which is a common pathogen causing hand, foot, and mouth disease in children. Currently, specific vaccines and drugs against CA16 are unavailable, and there is an unmet need to further understand the virus and invent effective treatment. Constructing a CA16 infectious clone with a reporter gene will greatly facilitate its virological studies. Here, we first reported the construction of a CA16 infectious clone (rCA16) whose progeny is highly replicative and virulent in suckling mice. On the basis of rCA16, we further inserted a NanoLuc (Nluc) reporter gene and made the rCA16-Nluc clone. We found that the Nluc gene in rCA16-Nluc is stable during continuous growing in Vero cells and thus allowed detection of a steady luciferase signal in rCA16-Nluc-infected Vero cells over 10 passages. Its application in antivirals characterization and high-throughput screening is exemplified by measuring IC50, CC50, and selection index of guanidine hydrochloride, ribavirin, chloroquine, and ammonium chloride against CA16. Finally, we showed that rCA16-Nluc based assay greatly simplified the CA16 neutralizing antibody tests. Thus, these two CA16 infectious clones will be robust tools for future enterovirus studies and antivirals development.

Good Steel Used in the Blade: Well-Tailored Type-I Photosensitizers with Aggregation-Induced Emission Characteristics for Precise Nuclear Targeting Photodynamic Therapy.

Photodynamic therapy (PDT) has long been recognized to be a promising approach for cancer treatment. However, the high oxygen dependency of conventional PDT dramatically impairs its overall therapeutic efficacy, especially in hypoxic solid tumors. Exploration of distinctive PDT strategy involving both high-performance less-oxygen-dependent photosensitizers (PSs) and prominent drug delivery system is an appealing yet significantly challenging task. Herein, a precise nuclear targeting PDT protocol based on type-I PSs with aggregation-induced emission (AIE) characteristics is fabricated for the first time. Of the two synthesized AIE PSs, TTFMN is demonstrated to exhibit superior AIE property and stronger type-I reactive oxygen species (ROS) generation efficiency owing to the introduction of tetraphenylethylene and smaller singlet-triplet energy gap, respectively. With the aid of a lysosomal acid-activated TAT-peptide-modified amphiphilic polymer poly(lactic acid)12k-poly(ethylene glycol)5k-succinic anhydride-modified TAT, the corresponding TTFMN-loaded nanoparticles accompanied with acid-triggered nuclear targeting peculiarity can quickly accumulate in the tumor site, effectively generate type-I ROS in the nuclear region and significantly suppress the tumor growth under white light irradiation with minimized systematic toxicity. This delicate "Good Steel Used in the Blade" tactic significantly maximizes the PDT efficacy and offers a conceptual while practical paradigm for optimized cancer treatment in further translational medicine.