Membrane intercalation-enhanced photodynamic inactivation of bacteria by a metallacycle and TAT-decorated virus coat protein

Abstract

Antibiotic resistance has become one of the major threats to global health. Photodynamic inactivation (PDI) develops little antibiotic resistance; thus, it becomes a promising strategy in the control of bacterial infection. During a PDI process, light-induced reactive oxygen species (ROS) damage the membrane components, leading to the membrane rupture and bacteria death. Due to the short half-life and reaction radius of ROS, achieving the cell-membrane intercalation of photosensitizers is a key challenge for PDI of bacteria. In this work, a tetraphenylethylene-based discrete organoplatinum(II) metallacycle (1) acts as a photosensitizer with aggregation-induced emission. It self-assembles with a transacting activator of transduction (TAT) peptide-decorated virus coat protein (2) through electrostatic interactions. This assembly (3) exhibits both ROS generation and strong membrane-intercalating ability, resulting in significantly enhanced PDI efficiency against bacteria. By intercalating in the bacterial cell membrane or entering the bacteria, assembly 3 decreases the survival rate of gram-negative Escherichia coli to nearly zero and that of gram-positive Staphylococcus aureus to ∼30% upon light irradiation. This study has wide implications from the generation of multifunctional nanomaterials to the control of bacterial infection, especially for gram-negative bacteria.

Beyond Antibiotics: Photo/Sonodynamic Approaches for Bacterial Theranostics

“…Targeted drug delivery accelerates the emergence of new AIE theranostic options. By taking advantage of bacteria-piloting agents (e.g., cationic groups, peptides, monoclonal antibodies), these "light-up" photosensitizers can be tailed with selective labeling, distinguishing, and killing of bacteria [73][74][75]. For example, the AIE photosensitizer after conjugation with positively charged zinc(II)dipicolylamine could specifically target to the negatively charged bacterial membrane via electrostatic interaction, but not to mammalian cells [76].…”

Recent Studies on the Antimicrobial Activity of Transition Metal Complexes of Groups 6–12

“…Within the series, compound 71 ( Figure 12) showed good activity against the pathogens with MIC values between 25 and 35 µg/mL. Finally, in 2019, Gao and coworkers published a bacterial membrane intercalation-enhanced photodynamic inactivation (PDI) system, of discrete organoplatinum(II) metallacycles (72, Figure 12) [144]. The compound acted as a photosensitizer with aggregation-induced emission.…”

Emissive Metallacycle‐Crosslinked Supramolecular Networks with Tunable Crosslinking Densities for Bacterial Imaging and Killing

“…[17] Moreover, the platinum(II) ligands and platinum(II) metallacycles also show the ability to inhibit bacterial growth. [18] Therefore, the antibacterial activities of supramolecular networks 5 a-c were further studied. Both Gram-positive (S. aureus) and Gram-negative (E. coli) bacteria were used to evaluate the antibacterial activities.…”