Phototheranostics has received sustained attention due to its great potential in revolutionizing conventional strategies of cancer treatment. However, trapped by the complexity, poor reproducibility, insufficient phototheranostic outputs, and inevitable damage to normal tissue of most multicomponent phototheranostic systems, its clinical translation has been severely hindered. Therefore, the exploration of “one for all” smart phototheranostic agents with versatile functionalities remains an appealing yet enormously challenging task. Herein, a reversibly pH-switchable and near-infrared second photosensitizer featuring aggregation-induced emission was tactfully designed by molecular engineering for precise tumor-targeting fluorescence imaging-guided phototherapy. Thanks to the strong intramolecular charge transfer, enhanced highly efficient intersystem crossing, and sufficient intramolecular motion, the developed agent DTTVBI was endowed with boosted type-I superoxide anion radical generation and excellent photothermal performance under 808 nm laser irradiation. More importantly, DTTVBI nanoparticles with high biocompatibility exhibit remarkably enhanced type-I photodynamic/photothermal therapy in the tumor region, thus offering significant antitumor effects both in vitro and in the patient-derived tumor xenograft model of colon cancer. This work sheds new light on the development of superior versatile phototheranostics for cancer therapy.
Multidrug resistance (MDR) bacteria pose a serious threat to human health. The development of alternative treatment modalities and therapeutic agents for treating MDR bacteria-caused infections remains a global challenge. Herein, a series of near-infrared (NIR) anion-𝝅 + photosensitizers featuring aggregation-induced emission (AIE-PSs) are rationally designed and successfully developed for broad-spectrum MDR bacteria eradication. Due to the strong intramolecular charge transfer (ICT) and enhanced highly efficient intersystem crossing (ISC), these electron-rich anion-𝝅 + AIE-PSs show boosted type I reactive oxygen species (ROS) generation capability involving hydroxyl radicals and superoxide anion radicals, and up to 99% photodynamic killing efficacy is achieved for both Methicillin-resistant Staphylococcus aureus (MRSA) and multidrug resistant Escherichia coli (MDR E. coli) under a low dose white light irradiation (16 mW cm −2 ). In vivo experiments confirm that one of these AIE-PSs exhibit excellent therapeutic performance in curing MRSA or MDR E. coli-infected wounds with negligible side-effects. The study would thus provide useful guidance for the rational design of high-performance type I AIE-PSs to overcome antibiotic resistance.
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.
Precise elimination of both Gram-positive and Gram-negative bacteria greatly contributes to the fight against bacterial infection but remains challenging. Herein, we present a series of phospholipid-mimetic aggregation-induced emission luminogens (AIEgens) that selectively kill bacteria by capitalizing on both the different structure of two bacterial membrane and the regulated length of substituted alkyl chains of AIEgens. Because of the positive charges that they contain, these AIEgens are able to kill bacteria by anchoring onto the bacterial membrane. For AIEgens with short alkyl chains, they could combine with the membrane of Gram-positive bacteria other than Gram-negative bacteria, because of their complicated outer layers, thus exhibiting selective ablation to Gram-positive bacteria. On the other hand, AIEgens with long alkyl chains have strong hydrophobicity with bacterial membranes, as well as large sizes. This inhibits the combination with Gram-positive bacterial membrane but destroys the membranes of Gram-negative bacteria, resulting in selective ablation to Gram-negative bacteria. Moreover, the combined processes to two bacteria are clearly observed by fluorescent imaging, and in vitro and in vivo experiments show the extraordinary antibacterial selectivity toward a Gram-positive and Gram-negative bacterium. This work could facilitate the development of species-specific antibacterial agents.
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/nearinfrared 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.
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