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

Significance Photodynamic inactivation (PDI), which has led to little antibiotic resistance, plays a promising role in the control of bacterial infection. Its main mechanism is the damage of membrane components by reactive oxygen species (ROS). However, achieving bacterial membrane intercalation of the photosensitizers remains a challenge. Here, we report the self-assembly of an aggregation-induced emission active photosensitizer with a cell-penetrating peptide-decorated virus coat protein. This assembly exhibits both ROS generation and a strong membrane-intercalating capacity, resulting in significantly enhanced PDI efficiency against bacteria. Especially for Escherichia coli possessing outer membrane, this assembly decreases the survival rate to nearly zero upon light irradiation. This study has implications from the control of bacterial infection to the generation of multifunctional nanomaterials. 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.