Mature biofilm-sensitive lysozyme-grafted Bi-guanidine backbone porphyrin nanorods for deep penetration and double phototherapy

Abstract

The efficacy of antibacterial therapy was largely vitiated because of the shield of bacteria by the intricate architecture of biofilms. For emerging phototherapy strategies like photothermal therapy (PTT) and photodynamic therapy (PDT), dense biofilms can substantially impede the permeation of photo-agents, ultimately compromising the thermal conductivity and reactive oxygen species (ROS) diffusion. To address these challenges, we have proposed a biofilm-sensitive MT nanorod with dual phototherapy, based on the ordered directional assembly of photosensitizer meso-tetra(4-carboxyphenyl) porphine (TCPP) molecules by metformin hydrochloride (MET) as functional backbone. The formed MT nanorod avoids the uncontrollable aggregation of TCPP, producing pleased water-solubility with efficient fluorescent emission and allowing simultaneous PTT-PDT effects under a single laser. The grafted MT-LYZ by conjugation of lysozyme (LYZ) to MT nanorods can be used for acidic environment guided deep biofilm penetration and LYZ-assisted dual phototherapy for effective elimination of mature biofilm, with MT-LYZ acquires adaptive conversion from negative to positive charges in biofilm. Because of effective bacterial ablation within biofilms and gene regulation in bacterial quorum, MT-LYZ was successfully utilized for the treatment of deep-seated MRSA biofilm infections with minimized side effects, which promotes the repair of the MRSA biofilm infected wounds in mice and displays anti-inflammatory features, providing an alternative approach for effectively combating biofilm infections.

Keywords: Biofilm infection; Biofilm-sensitive; Deep penetration; Phototheranostic agents; Synergistic therapy.