No abstract

The intricate environment of biofilms provides a heaven for bacteria to escape antibiotic eradication, leading to persistent chronic infections. Therefore, it is urgently needed to develop effective therapies to combat biofilm‐associated infections. To address this problem, a series of antimicrobial agents are designed and synthesized utilizing triphenylamine imidazole silver complexes (TPIMS). Due to the photoactivated release of Ag+ coupled with aggregation‐induced emission (AIE) properties and efficient 1O2 generation, TPIMS exhibits excellent visual diagnostic capabilities and potent broad‐spectrum antimicrobial activity, showing antimicrobial efficacy against both Gram (+) and Gram (−) bacteria. Additionally, TPIMS shows extraordinary antibacterial performance and biofilm resistance against methicillin‐resistant Staphylococcus aureus (MRSA), with reduced potential for resistance thanks to the synergistic effect of phototoxicity and dark toxicity. Notably, among the TPIMS variants tested, TPIMS‐8 has demonstrated exceptional curative ability against resistant bacterial biofilm infections in vivo with minimal side effects. Furthermore, it is applied to clinical samples from infected patients and the results indicated that TPIMS‐8 is able to achieve excellent bacterial‐specific detection and superior killing of drug‐resistant bacteria even in complex systems, demonstrating its great potential for clinical applications. This study presents a promising foundation for the development of advanced antimicrobial therapeutics targeting multidrug‐resistant bacteria and biofilm‐associated infections.

Anticancer drug development is important for human health, yet it remains a tremendous challenge. Photodynamic therapy (PDT), which induces cancer cell apoptosis via light-triggered production of reactive oxygen species, is a promising method. However, it has minimal efficacy in subcellular targeting, hypoxic microenvironments, and deep-seated malignancies. Here, we constructed a breast cancer photo-activable theranostic nanosystem through the rational design of a synthetic lysosomal-targeted molecule with multifunctions as aggregation-induced near-infrared (NIR) emission, a photosensitizer (PDT), and organosilver (chemotherapy) for NIR imaging and synergistic cancer therapy. The synthetic molecule could self-assemble into nanoparticles (TPIMBS NPs) and be stabilized with amphiphilic block copolymers for enhanced accumulation in tumor sites through passive targeting while reducing the leakage in normal tissues. Through photochemical internalization, TPIMBS NPs preferentially concentrated in the lysosomes of cancer cells and generated reactive oxygen species (ROS) upon light irradiation, resulting in lysosomal rupture and release of PSs to the cytosol, which led to cell apoptosis. Further, the photoinduced release of Ag+ from TPIMBS NPs could act as chemotherapy, significantly improving the overall therapeutic efficacy by synergistic effects with PDT. This research sheds fresh light on the creation of effective cancer treatments.

The emergence of antibiotic-resistant “superbugs” poses a serious threat to human health. Nanomaterials and cationic polymers have shown unprecedented advantages as effective antimicrobial therapies due to their flexibility and ability to interact with biological macromolecules. They can incorporate a variety of antimicrobial substances, achieving multifunctional effects without easily developing drug resistance. Herein, this article discusses recent advances in cationic polymers and nano-antibacterial materials, including material options, fabrication techniques, structural characteristics, and activity performance, with a focus on their fundamental active elements.

The formation of microbial biofilms is acknowledged as a major virulence factor in a range of persistent local infections. Failures to remove biofilms with antibiotics foster the emergence of antibiotic-resistant bacteria and result in chronic infections. As a result, the construction of effective biofilm-inhibiting and biofilm-eradicating chemicals is urgently required. Herein, we designed a water-soluble probe APDIS for membrane-active fluorescence and broad-spectrum antimicrobial actions, particularly against methicillin-resistant Staphylococcus aureus (MRSA), which shows multidrug resistance. In vitro and in vivo experiments demonstrate its high antibacterial effects comparable to vancomycin. Furthermore, it inhibits biofilm formation by effectively killing planktonic bacteria at low inhibitory concentrations, without toxicity to mammalian cells. More importantly, this probe can efficiently penetrate through biofilm barriers and exterminate bacteria that are enclosed within biofilms and startle existing biofilms. In the mouse model of implant-related biofilm infections, this probe exhibits strong antibiofilm activity against MRSA biofilms, thus providing a novel theranostic strategy to disrupt biofilms in vivo effectively. Our results indicate that this probe has the potential to be used for the development of a combinatorial theranostic platform with synergistic enhanced effects for the treatment of multidrug-resistant bacterial infections and antibiofilm medications.