Pseudomonas aeruginosa targeting cascade photodynamic nanoassemblies for efficient antibacterial and anti-inflammatory therapy

Natural resistance and biofilm formation make Pseudomonas aeruginosa (P. aeruginosa) highly infectious worldwide. Fighting against P. aeruginosa in biofilms has been a long challenge. Herein, P. aeruginosa-targeting nanoassemblies (PGPF@ICG) are designed by encapsulating indocyanine green (ICG) into farnesol-decorated poly(D-glucose)-block-poly(hydroxyethyl methylacrylate) (denoted PGPF). First, PGPF@ICG can effectively permeate into the biofilm of P. aeruginosa and subsequently target LecA. Under 808 nm laser irradiation, PGPF@ICG can change membrane potentials and improve the ROS level of internal bacteria and biofilms to effectively kill P. aeruginosa and eliminate biofilms. Meanwhile, farnesol released from PGPF by the cleavage of the oxalic bond in the inflammatory environment further reinforced antibacterial efficacy and remodelled the inflammatory environment by downregulating M1 macrophages and their related inflammatory factors. Through infected site delivery, PGPF@ICG+NIR showed antibacterial and anti-inflammatory effects superior to those of the other groups in P. aeruginosa-infected wound and subcutaneous cyst models. Furthermore, the innate immune response of the infected site is remodelled by PGPF@ICG+NIR, as evidenced by accelerating the healing of the infected site and new angiogenesis, as well as reducing inflammation. Therefore, the biocompatible PGPF@ICG targets biofilms and bacteria, as well as remodels innate immunity in a cascade manner, providing a new strategy for the treatment of P. aeruginosa-infected diseases.