ε‐poly‐L‐lysine‐modified polydopamine nanoparticles for targeted photothermal therapy of drug‐resistant bacterial keratitis

Abstract

Bacterial keratitis can lead to intraocular infection and even blindness without prompt and potent treatments. Currently, clinical abuse of antibiotics encouraged the evolution of resistant bacteria. Conventional antibiotic eye drops based keratitis treatment has been heavily restricted due to the lack of bactericidal efficiency and easy induction of bacterial resistance. Hence, developing an effective treatment strategy for bacterial keratitis is of great significance. In this work, we investigated ε‐poly‐ l ‐lysine (EPL)‐modified polydopamine (PDA) nanoparticles (EPL@PDA NPs)‐mediated antibacterial photothermal therapy (aPTT), to cope with methicillin‐resistant Staphylococcus aureus (MRSA)‐induced keratitis. The surface modification of cationic peptide EPL enables EPL@PDA NPs to specifically target negatively charged MRSA and induces local hyperthermia to kill the bacteria under low ambient temperature. Under near‐infrared (NIR) irradiation, the sterilization efficiency of EPL@PDA NPs suspension for MRSA in vitro was up to 99.96%. The EPL@PDA‐mediated aPTT presented potent antibacterial efficacy in treating MRSA‐induced keratitis with little corneal epithelial cytotoxicity and good biocompatibility. In conclusion, the bacterial‐targeting aPTT platform in this work provides a prospective method for the management of MRSA‐induced refractory bacterial keratitis.

Multifunctional Polymer Vesicles for Synergistic Antibiotic–Antioxidant Treatment of Bacterial Keratitis

“…The half of corneal epithelium was shaved, and three superficial stromal incisions were made with a scalpel. Then, 10 μL S. aureus suspension (3–5 × 10 8 CFU/mL) was inoculated onto the corneas for bacterial infection. , Twenty-4 h after infection, the mice were randomized into 6 groups (n = 6) and 7-day course of treatment was carried out (5 μL per eye twice daily with PBS, PAM, CIP@PAM, PPM, CIP@PPM, and CIP, respectively). The CIP@PPM, CIP@PAM and CIP groups contained almost the same dose of CIP.…”

Functional insights to the development of bioactive material for combating bacterial infections

“…Second, the antimicrobial polymers spread through the cell wall and are adsorbed into the cell membrane, which eventually leads to the destruction of the cell membrane, resulting in the leakage of bacterial intracellular components and bacterial death. Poly-(α-aminoacids) (Engler et al, 2011;Hou et al, 2017), cationic polycarbonates (Yuen et al, 2017;Tan et al, 2020), phosphonium polymers (Loczenski Rose et al, 2017;Cuthbert et al, 2018;Palermo et al, 2019), chitosan-based cationic polysaccharides, quaternary ammonium salts (Li et al, 2021a), ε-poly-L-lysine (ε-PL) (Fan et al, 2023) are some examples of positively charged polymers with antibacterial properties.…”

Universal and One-Step Modification to Render Diverse Materials Bioactivation

“…Polydopamine (PDA) coating is one of the most widely used methods for versatile surface modification. , PDA, as a primer layer, can be further modified with bioactive molecules that contain thiol or amine groups to have Michael-type addition or Schiff-base formations. , Although PDA coating has been widely used, it is complicated due to the promiscuous reactivity of phenolic chemistry, − causing nonspecific conjugation of proteins and macromolecules. , In addition, the two-step method generally requires a long deposition time of over 12–24 h, and the characteristic dark color of the PDA coating reduces patients’ psychological acceptance for its application in implant biomaterials . An alternative strategy introduces repeating residues of 3,4-dihydroxy- l -phenylalanine (DOPA) and lysine into functional peptides or polymers to achieve diversified surface modification via a simple one-step method. − To tether the bioactive molecules to material surfaces stably, the anchoring peptides generally require multiple catechol-containing DOPA and amine-containing residues, usually using lysine. , However, the anchoring peptides are dominantly prepared via time-consuming solid-phase synthesis, which is difficult to achieve large-scale production and limits the application of this strategy to obtain bioactive materials from bioinert materials.…”

“…18,19 PDA, as a primer layer, can be further modified with bioactive molecules that contain thiol or amine groups to have Michael-type addition or Schiff-base formations. 20,21 Although PDA coating has been widely used, it is complicated due to the promiscuous reactivity of phenolic chemistry, 22−24 causing nonspecific conjugation of proteins and macromolecules. 25,26 In addition, the two-step method generally requires a long deposition time of over 12−24 h, and the characteristic dark color of the PDA coating reduces patients' psychological acceptance for its application in implant biomaterials.…”