Chlorin e6 (Ce6)-loaded supramolecular polypeptide micelles with enhanced photodynamic therapy effect against Pseudomonas aeruginosa

Gram-negative bacterial infection remains an instant health threat in the world owing to the shortage of effective and biocompatible drugs. Recently, photodynamic therapy (PDT) has attracted considerable attention, capable of treating bacterial infections with little drug-resistance. However, it also has some limitations, such as the limited diffusion distance, the short lifetime of reactive oxygen species (ROS), and poor sensitivity to Gram-negative bacteria. Thus, PDT, as a local treatment method, is bound to be combined with the targeting technology to enhance its membrane-capturing ability. Herein, we fabricated new polymeric micelles with the bacteria-targeting ability, high adherence, and photosensitizer (PS)-loading capacity that can be adsorbed onto the bacterial membrane to enhance the PDT efficiency. In this paper, a novel photodynamic drug delivery system was obtained by the supramolecular assembly of chlorin e6 (Ce6)-conjugated alpha-cyclodextrin (alpha-CD) and polyethylene glycol (PEG)ylated polypeptide (Pep). These cationic Pep@Ce6 micelles showed great efficacy to eradicate biofilms and inactivate persister cells with negligible toxicity towards mammalian cells. Furthermore, in vivo therapeutic performance was identified by the prominent antibacterial ability and good wound healing capacity in a P. aeruginosa-infected skin knife injury model. This research is of great significance for the preparation of multifunctional nanomaterials and the treatment of bacterial infections, especially those caused by Gram-negative bacteria.

Automated summary

Gram-negative bacterial infection is still a global health threat due to lack of effective drugs. Photodynamic therapy (PDT) has shown potential in treating these infections, but has limitations and needs to be combined with targeting technology. This study developed a novel PDT drug delivery system with bacteria-targeting ability, high disinfection efficacy, and low toxicity to mammalian cells, showing promising results in treating infections caused by Gram-negative bacteria.