title: Antimicrobial peptide-modified liposomes for bacteria targeted delivery of temoporfin in photodynamic antimicrobial chemotherapy.
abstract: Photodynamic antimicrobial chemotherapy (PACT) and antimicrobial peptides (AMPs) are two promising strategies to combat the increasing prevalence of antibiotic-resistant bacteria. To take advantage of these two strategies, we integrated a novel antimicrobial peptide (WLBU2) and a potent generation II photosensitizer (temoporfin) into liposomes by preparing WLBU2-modified liposomes, aiming at bacteria targeted delivery of temoporfin for PACT. WLBU2 was successfully coupled to temoporfin-loaded liposomes using a functional phospholipid. The delivery of temoporfin to bacteria was confirmed by fluorescence microscopy and flow cytometry, thus demonstrating that more temoporfin was delivered to bacteria by WLBU2-modified liposomes than by unmodified liposomes. Consequently, the WLBU2-modified liposomes eradicated all methicillin-resistant Staphylococcus aureus (MRSA) and induced a 3.3 log(10) reduction of Pseudomonas aeruginosa in the in vitro photodynamic inactivation test. These findings demonstrate that the use of AMP-modified liposomes is promising for bacteria-targeted delivery of photosensitizers and for improving the PACT efficiency against both gram-positive and gram-negative bacteria in the local infections.
authors.affiliation: Department of Pharmaceutical Technology, Friedrich-Schiller-University Jena, Lessingstrasse 8, D-07743, Jena, Germany.
authors.forename: Kewei
authors.initials: K
authors.lastname: Yang
authors.forename: Burkhard
authors.initials: B
authors.lastname: Gitter
authors.forename: Ronny
authors.initials: R
authors.lastname: Rüger
authors.forename: Gerhard D
authors.initials: GD
authors.lastname: Wieland
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.forename: Xiangli
authors.initials: X
authors.lastname: Liu
authors.forename: Volker
authors.initials: V
authors.lastname: Albrecht
authors.forename: Alfred
authors.initials: A
authors.lastname: Fahr
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D001419:Bacteria / Q000187:drug effects*; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D005434:Flow Cytometry; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008081:Liposomes / Q000737:chemistry*; D008652:Mesoporphyrins / Q000737:chemistry / Q000494:pharmacology*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008856:Microscopy, Fluorescence; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects
chemical_list: D023181:Antimicrobial Cationic Peptides; D008081:Liposomes; D008652:Mesoporphyrins; D017319:Photosensitizing Agents; C520840:WLBU2 peptide; C072269:temoporfin